Research Article Genetic Variations of Cytokines and ...
Transcript of Research Article Genetic Variations of Cytokines and ...
Research ArticleGenetic Variations of Cytokines and Cytokine Receptors inPsoriasis Patients from China
Xiao-Lan Li1 Chun-Feng Wu2 and Gui-Sheng Wu2
1 Department of Dermatology and Rheumatology Affiliated Yanrsquoan Hospital of Kunming Medical CollegeKunming Yunnan 650051 China
2 State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyThe Chinese Academy of Sciences Kunming Yunnan 650201 China
Correspondence should be addressed to Xiao-Lan Li lixiaolan96hotmailcom and Gui-Sheng Wu wuguishengmailkibaccn
Received 20 March 2014 Accepted 11 May 2014 Published 25 May 2014
Academic Editor Ji-Fu Wei
Copyright copy 2014 Xiao-Lan Li et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Psoriasis is a chronic inflammatory and hyperproliferative skin disease affected by both genetic and environmental factors Theaim of the present study was to investigate polymorphisms in a candidate gene family of interleukin (IL) in unrelated Chinesepatients with psoriasis and control subjects without psoriasis In this case-control study 200 unrelated Chinese psoriasis patientsand 298 age- and sex-matched control subjects were enrolled Genomic DNA was prepared from peripheral blood obtained fromall psoriasis patients and control subjects We genotyped seven single-nucleotide polymorphisms (SNPs) in candidate genes ofsix ILs IL4 IL10 IL12B IL13 IL15 and IL23R which have been shown in the literature to be associated with psoriasis in otherethnic groups Among the seven SNPs in the six IL genes studied only the rs3212227 in the IL12B gene was found to be associatedwith psoriasis at genotypic level in the studied population The CC genotype in the IL12B gene is a protective factor of psoriasis(119875 = 00218 OR = 051 95 CI 027ndash096) in Chinese Furthermore the studied Chinese population has extremely low minorallele frequency for IL23R Together the data reveal unique genetic patterns in Chinese that may be in part responsible for thelower risk for psoriasis in this population
1 Introduction
Psoriasis is an immunologically mediated chronic inflam-matory and hyperproliferative skin disease affected by bothgenetic and environmental factors The prevalence of psori-asis varied among populations with different genetic back-grounds and habitats from 3 inNorthern Europe and 2 inNorth America and the UK to 01ndash03 in American Indiansand East Asia [1 2] Psoriasis is proposed to be associatedwith other immune diseases such as arthritis and Crohnrsquosdisease [3] Initial causative research has identified strongassociation between psoriasis and the interleukin genes (IL4IL10 IL12B IL13 and IL23R) in the northern European fromUS and UK [4ndash7] Furthermore the SNP rs56245420 in theIL15 gene has been found to be associatedwith psoriasis in theChinese Han population but not in any of the UK Germanor US Caucasian populations investigated [8ndash10] since theminor allele frequency for this SNP and others across IL15
differs quite strikingly between the populations suggestingheterogeneity in the genetic susceptibility to psoriasis
In this study we aimed to determine if psoriasis isassociatedwith six IL genes that have been strongly associatedwith psoriasis in Europeans but not well studied in ChineseThe seven included SNPs are rs2243250 in the IL4 geners1800872 in the IL10 gene rs3212227 in the IL12B geners1800925 and rs20541 in the IL13 gene rs56245420 in the IL15gene and rs11209026 in the IL23R gene
2 Materials and Methods
21 Study Population A total of 200 psoriasis patients and298 healthy controls were recruited in this study (see Table 2)All participants did not suffer from any other diseases andbelonged to Han nationality in Yunnan Province China Thestudy was performed according to the Helsinki Declaration
Hindawi Publishing CorporationInternational Journal of GenomicsVolume 2014 Article ID 870597 5 pageshttpdxdoiorg1011552014870597
2 International Journal of Genomics
Table1Prim
ersequ
encesPC
Rprod
uctlengthsrestrictio
nendo
nucle
asesand
restric
tionpatte
rnsfor
theP
CR-RFL
Panalyzed
SNPs
SNP
Gene
Positionof
SNP
ingeno
mic
sequ
ence
Forw
ardprim
era
Reversep
rimer
Ann
eal
temperature
(∘C)
Prod
uct
leng
th(bp)
Restr
ictio
nendo
nucle
ases
Fragmentsof
frequ
entallele
geno
type
(bp)
Fragmentsof
heterozygous
geno
type
(bp)
Fragmentsof
rare
allele
geno
type
(bp)
Reference
rs2243250
IL4
132009154CT
TAAAC
TTGGGAG
AAC
ATGGT
TGGGGAAAG
ATAG
AGTA
ATA
49195
AvaII
195
22+173+195
22+173
[1]
rs1800872
IL10
206946
407AC
AGGTG
ATGTA
ATAT
CTCT
GT
TAAAT
ATCC
TCAAAG
TTCC
57303
RsaI
65+238
65+238+303
303
[2]
rs3212227
IL12B
158742950AC
TTCT
ATCT
GAT
TTGCT
TTA
TGAAAC
ATTC
CATA
CATC
C51
233
TaqI
233
68+165+233
68+165
[3]
rs1800
925
IL13
131992809CT
GTC
GCC
TTTT
CCTG
CTCT
TCCC
GC
GGAAT
CCAG
CATG
CCTT
GTG
AGG
65247
Bsh1236I
23+224
23+224+247
247
[4]
rs20541
IL13
13199596
4CT
TAGGCT
GAAG
ACGGGCA
GCA
AAG
AAAC
TTTT
TCGCG
AGGGC C
63199
MspI
22+177
22+177+199
199
[5]
rs56245420
IL15
142873720AT
TTTC
TGTT
ATTA
ACAAAC
ATCA
CTCT
GCA
ACAC
TTGTA
CATA
TTTT
TATT
CAAT A
T54
274
SspI
27+247
27+247+274
274
Thisstu
dya M
ismatch
isshow
nin
bold
andun
derlinedfont
International Journal of Genomics 3
Table 2 Genotyping of seven studied SNPs in psoriasis patients (119899 = 200) and controls (119899 = 298)
SNP Gene Population Genotype () Minor allele ()
rs2243250 IL4TT TC CC C
Controls 189 (634) 98 (329) 11 (37) 120 (201)Psoriasis 127 (635) 61 (305) 12 (60) 85 (213)
rs1800872 IL10AA AC CC C
Controls 138 (463) 123 (413) 37 (124) 197 (331)Psoriasis 93 (465) 86 (430) 21 (105) 128 (320)
rs3212227 IL12BAA AC CC C
Controls 119 (399) 128 (430) 51 (171) 230 (386)Psoriasis 77 (385) 104 (520) 19 (95)lowasta 142 (355)
rs1800925 IL13CC CT TT T
Controls 222 (745) 72 (242) 4 (13) 80 (134)Psoriasis 140 (700) 52 (260) 8 (40) 68 (170)
rs20541 IL13CC CT TT T
Controls 146 (490) 126 (423) 26 (87) 178 (299)Psoriasis 100 (500) 80 (400) 20 (100) 120 (300)
rs56245420 IL15AA AT TT T
Controls 139 (466) 135 (453) 24 (81) 183 (307)Psoriasis 78 (390) 97 (485) 25 (125) 147 (368)
rs11209026 IL23RGG GA AA A
Controls 298 (100) 0 0 0Psoriasis 200 (100) 0 0 0
lowasta119875 = 00218
with approval of the institutional review boards of the Affil-iated Yanrsquoan Hospital of Kunming Medical College and theKunming Institute of Botany Informed consent was obtainedfrom each participant before inclusion in this study
22 Determination of Genotype Genomic DNAs were iso-lated from whole blood using regular phenolchloroformmethod The SNP rs11209026 in the IL23R gene was geno-typed by the TaqMan allelic discrimination method (AppliedBiosystems) New PCR-RFLP methods were generated togenotype the SNP rs56245420 in the IL15 gene Primers 51015840-TTTCTGTTATTAACAAACATCACTCTG-31015840 and 51015840-CAACAC TTG TAC ATA TTT TTA TTC AAt AT-31015840 (mismatchis shown in bold lower case) were used for rs56245420 Otherfive SNPs were genotyped by PCR-RFLP methods describedpreviously with slight modification [11ndash15] PCR reactionwas carried out in a total volume of 20 120583L containing 20 ngof genomic DNA 1 times PCR buffer 15mMMgCl
2 200120583M
of each dNTP 30 ng of each primer and 1 unit of TaqDNA polymerase (TakaRa) Samples were denatured at 95∘Cfor 2min followed by 30 cycles of 94∘C for 45 sec 61∘C(rs2395029) or 54∘C (rs56245420) for 45 sec and 72∘C for45 sec and endedwith a final extension for 7min at 72∘C PCRproducts were digested with 4U of appropriate restrictionendonuclease and electrophoresed on 3 agarose gels andstained with ethidium bromide The restriction endonucle-ases PCR product lengths and restriction patterns are shownin Table 1
23 Data Analysis Statistics analysis was performed by SPSSsoftware for windows (SPSS Inc) The frequencies of geno-types and alleles for all the six studied loci were determinedassuming codominant inheritance The Hardy-Weinbergequilibrium (HWE) for six loci in psoriasis patients andcontrols was tested by means of chi-square tests The statis-tical significance of the genotype and allele frequency vari-ables between the psoriasis patients and control group wasevaluated by chi-square test with Yates correction for smallnumbers Relative risk associated with the significant geno-type was estimated by the odds ratio (OR) OR with 95confidence intervals (95 CI) was tested using a chi-squaredistribution and the null hypothesis being tested is OR = 1 119875values lt005 were considered as statistically significant
3 Results
Only one of the fourteen Hardy-Weinberg tests (seven poly-morphic loci each in the psoriasis patient and control groups)had 119875 values smaller than 005 (119875 = 001 at rs3212227in controls) All nine remaining genotype frequencies fitHardy-Weinberg expectations according to chi-square testsin psoriasis patients and controls (119875 gt 005) Therefore thereis no meaningful deviation from WHE and our populationis derived from random mating
Polymorphism (minor allele frequency gt 1) has beenfound for all studied SNPs except for rs11209026 in the IL23Rgene (Table 2) Table 2 shows that rs3212227 in the IL12B gene
4 International Journal of Genomics
Table 3 Correlation of psoriasis symptoms with SNPs in the IL genes
SNP Genotype Psoriasis Controls OR (95 CI) Allele Psoriasis Controls OR (95 CI)
rs2243250
TT 127 189 T 315 476TC 61 98 093 (063ndash137) C 85 120 107 (078ndash146)CC 12 11 162 (069ndash378)
TC-CC 73 109 100 (069ndash145)
rs1800872
AA 93 138 A 272 399AC 86 123 104 (071ndash152) C 128 197 095 (072ndash125)CC 21 37 084 (046ndash153)
AC-CC 107 160 099 (069ndash142)
rs3212227
CC 19 51 C 142 230AC 104 128 218 (121ndash392) A 258 366 114 (088ndash148)AA 77 119 171 (096ndash317)
AC-AA 181 247 197 (112ndash345)
rs1800925
CC 140 222 C 332 516CT 52 72 115 (076ndash174) T 68 80 132 (093ndash186)TT 8 4 317 (094ndash1072)
CT-CC 60 76 125 (084ndash186)
rs20541
CC 100 146 C 280 418CT 80 126 093 (064ndash136) T 120 178 101 (077ndash133)TT 20 26 112 (059ndash212)
CT-TT 100 152 096 (067ndash137)
rs56245420
AA 78 139 A 253 413AT 97 135 128 (087ndash187) T 147 183 128 (100ndash171)TT 25 24 185 (099ndash346)
AT-TT 122 159 136 (094ndash196)
(119875 = 00218) was associated with psoriasis at genotypic levelin the studied population Other SNPs examined were notassociated with psoriasis considered from single locus Asshown in Table 3 while the AC genotype (OR = 148 95CI 095ndash230) and the alleles (OR = 084 95 CI 063ndash113)at rs3212227 in the IL12B were not a risk factor of psoriasisthe CC genotype was a protective factor of psoriasis (OR =051 95 CI 027ndash096)
4 Discussion
The etiology of psoriasis is a complex interaction of envi-ronmental and biological factors Genetic factors may playa significant role in the risk of psoriasis in Chinese [10 16]Recent genetic studies indicate that the location of these genesvaries considerably among populations and families We areinterested to know if psoriasis is associatedwith the genes thathave been strongly associated with psoriasis in Europeans butnot well studied in Chinese
Our results showed that the IL12B gene was associatedwith psoriasis in Chinese at genotypic level (119875 lt 005) whichis in line with the findings from European studies [17] TheCC genotype for rs3212227 in IL12B is a protective factor(OR = 051) from psoriasis Similar result from studying SNPrs6887695 in IL12B showed that the minor allele C was aprotective factor from psoriasis [5]
The nonsynonymous SNP in IL23R rs11209026 widelythought to be the primary psoriasis-associated SNP in IL23Rin Europeans was found not to be polymorphic in Chinesewhich is in agreementwith the findings of others [18]The lowfrequencies of variant in IL23R are accordingly of low risk forpsoriasis in ChineseWith single SNP analysis no associationis found between the psoriasis and the IL4 IL10 IL13 andIL15 genes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Thisworkwas supported byGrants from theNationalNaturalScience Foundation of China (81360457) and the NaturalScience Foundation of Yunnan Province (2012FB099)
References
[1] J E Gudjonsson and J T Elder ldquoPsoriasis epidemiologyrdquoClinics in Dermatology vol 25 no 6 pp 535ndash546 2007
[2] R Parisi D P Symmons C E Griffiths and D M AshcroftldquoGlobal epidemiology of psoriasis a systematic review of
International Journal of Genomics 5
incidence and prevalencerdquo Journal of Investigative Dermatologyvol 133 no 2 pp 377ndash385 2013
[3] R P Nair T Henseler S Jenisch et al ldquoEvidence for twopsoriasis susceptibility loci (HLA and 17q) and two novelcandidate regions (16q and 20p) by genome-wide scanrdquoHumanMolecular Genetics vol 6 no 8 pp 1349ndash1356 1997
[4] K C Duffin andG G Krueger ldquoGenetic variations in cytokinesand cytokine receptors associated with psoriasis found bygenome-wide associationrdquo Journal of Investigative Dermatologyvol 129 no 4 pp 827ndash833 2009
[5] Y Liu C Helms W Liao et al ldquoA genome-wide associationstudy of psoriasis and psoriatic arthritis identifies new diseaselocirdquo PLoS Genetics vol 4 no 3 2008
[6] R P Nair K C Duffin C Helms et al ldquoGenome-wide scanreveals association of psoriasiswith IL-23 andNF-120581BpathwaysrdquoNature Genetics vol 41 no 2 pp 199ndash204 2009
[7] F Capon M J Bijlmakers N Wolf et al ldquoIdentificationof ZNF313RNF114 as a novel psoriasis susceptibility generdquoHuman Molecular Genetics vol 17 no 13 pp 1938ndash1945 2008
[8] R L Smith S Eyre R BWarrenH S Young C EMGriffithsand J Worthington ldquoNo association between polymorphismsin the interleukin-15 gene and early-onset psoriasis in a UKcohort suggests heterogeneity for this susceptibility locus iden-tified in Chinese psoriasis patientsrdquo Journal of InvestigativeDermatology vol 128 no 12 pp 2904ndash2905 2008
[9] W Weger A Hofer P Wolf et al ldquoRole of the interleukin15 96516AgtT and IL15 96330CgtA gene polymorphisms incaucasian patients with chronic plaque psoriasisrdquo Journal ofDermatological Science vol 51 no 2 pp 147ndash149 2008
[10] X J Zhang K L Yan Z M Wang et al ldquoPolymorphismsin interleukin-15 gene on chromosome 4q312 are associatedwith psoriasis vulgaris in Chinese populationrdquo Journal ofInvestigative Dermatology vol 127 no 11 pp 2544ndash2551 2007
[11] E Tarazona-Santos and S A Tishkoff ldquoDivergent patterns oflinkage disequilibrium and haplotype structure across globalpopulations at the interleukin-13 (IL13) locusrdquo Genes andImmunity vol 6 no 1 pp 53ndash65 2005
[12] P E Graves M Kabesch M Halonen et al ldquoA cluster of seventightly linked polymorphisms in the IL-13 gene is associatedwith total serum IgE levels in three populations of whitechildrenrdquo Journal of Allergy and Clinical Immunology vol 105no 3 pp 506ndash513 2000
[13] T Kawashima E Noguchi T Arinami et al ldquoLinkage andassociation of an interleukin 4 gene polymorphism with atopicdermatitis in Japanese familiesrdquo Journal ofMedical Genetics vol35 no 6 pp 502ndash504 1998
[14] C C Mok J S Lanchbury D W Chan and C S LauldquoInterleukin-10 promoter polymorphisms in Southern Chinesepatients with systemic lupus erythematosusrdquo Arthritis andRheumatology vol 41 no 6 pp 1090ndash1095 1998
[15] A Alvarado-NavarroMMontoya-Buelna J FMunoz-Valle RI Lopez-Roa C Guillen-Vargas and M Fafutis-Morris ldquoThe31015840UTR 1188 AC polymorphism in the interleukin-12p40 gene(IL-12B) is associated with lepromatous leprosy in the West ofMexicordquo Immunology Letters vol 118 no 2 pp 148ndash151 2008
[16] F Long C Sun D Deng X Zhou X P Li and Y P ZhangldquoTNF-238A is associated with juvenile onset psoriasis inpatients of Han population in Southwest Chinardquo Journal ofDermatological Science vol 36 no 2 pp 109ndash111 2004
[17] F Capon S Semprini B Dallapiccola and G Novelli ldquoEvi-dence for interaction between psoriasis-susceptibility loci on
chromosomes 6p21 and 1q21rdquo The American Journal of HumanGenetics vol 65 no 6 pp 1798ndash1800 1999
[18] S I Davidson X Wu Y Liu et al ldquoAssociation of ERAP1but not IL23R with ankylosing spondylitis in a Han ChinesepopulationrdquoArthritis and Rheumatism vol 60 no 11 pp 3263ndash3268 2009
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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International Journal of
Microbiology
2 International Journal of Genomics
Table1Prim
ersequ
encesPC
Rprod
uctlengthsrestrictio
nendo
nucle
asesand
restric
tionpatte
rnsfor
theP
CR-RFL
Panalyzed
SNPs
SNP
Gene
Positionof
SNP
ingeno
mic
sequ
ence
Forw
ardprim
era
Reversep
rimer
Ann
eal
temperature
(∘C)
Prod
uct
leng
th(bp)
Restr
ictio
nendo
nucle
ases
Fragmentsof
frequ
entallele
geno
type
(bp)
Fragmentsof
heterozygous
geno
type
(bp)
Fragmentsof
rare
allele
geno
type
(bp)
Reference
rs2243250
IL4
132009154CT
TAAAC
TTGGGAG
AAC
ATGGT
TGGGGAAAG
ATAG
AGTA
ATA
49195
AvaII
195
22+173+195
22+173
[1]
rs1800872
IL10
206946
407AC
AGGTG
ATGTA
ATAT
CTCT
GT
TAAAT
ATCC
TCAAAG
TTCC
57303
RsaI
65+238
65+238+303
303
[2]
rs3212227
IL12B
158742950AC
TTCT
ATCT
GAT
TTGCT
TTA
TGAAAC
ATTC
CATA
CATC
C51
233
TaqI
233
68+165+233
68+165
[3]
rs1800
925
IL13
131992809CT
GTC
GCC
TTTT
CCTG
CTCT
TCCC
GC
GGAAT
CCAG
CATG
CCTT
GTG
AGG
65247
Bsh1236I
23+224
23+224+247
247
[4]
rs20541
IL13
13199596
4CT
TAGGCT
GAAG
ACGGGCA
GCA
AAG
AAAC
TTTT
TCGCG
AGGGC C
63199
MspI
22+177
22+177+199
199
[5]
rs56245420
IL15
142873720AT
TTTC
TGTT
ATTA
ACAAAC
ATCA
CTCT
GCA
ACAC
TTGTA
CATA
TTTT
TATT
CAAT A
T54
274
SspI
27+247
27+247+274
274
Thisstu
dya M
ismatch
isshow
nin
bold
andun
derlinedfont
International Journal of Genomics 3
Table 2 Genotyping of seven studied SNPs in psoriasis patients (119899 = 200) and controls (119899 = 298)
SNP Gene Population Genotype () Minor allele ()
rs2243250 IL4TT TC CC C
Controls 189 (634) 98 (329) 11 (37) 120 (201)Psoriasis 127 (635) 61 (305) 12 (60) 85 (213)
rs1800872 IL10AA AC CC C
Controls 138 (463) 123 (413) 37 (124) 197 (331)Psoriasis 93 (465) 86 (430) 21 (105) 128 (320)
rs3212227 IL12BAA AC CC C
Controls 119 (399) 128 (430) 51 (171) 230 (386)Psoriasis 77 (385) 104 (520) 19 (95)lowasta 142 (355)
rs1800925 IL13CC CT TT T
Controls 222 (745) 72 (242) 4 (13) 80 (134)Psoriasis 140 (700) 52 (260) 8 (40) 68 (170)
rs20541 IL13CC CT TT T
Controls 146 (490) 126 (423) 26 (87) 178 (299)Psoriasis 100 (500) 80 (400) 20 (100) 120 (300)
rs56245420 IL15AA AT TT T
Controls 139 (466) 135 (453) 24 (81) 183 (307)Psoriasis 78 (390) 97 (485) 25 (125) 147 (368)
rs11209026 IL23RGG GA AA A
Controls 298 (100) 0 0 0Psoriasis 200 (100) 0 0 0
lowasta119875 = 00218
with approval of the institutional review boards of the Affil-iated Yanrsquoan Hospital of Kunming Medical College and theKunming Institute of Botany Informed consent was obtainedfrom each participant before inclusion in this study
22 Determination of Genotype Genomic DNAs were iso-lated from whole blood using regular phenolchloroformmethod The SNP rs11209026 in the IL23R gene was geno-typed by the TaqMan allelic discrimination method (AppliedBiosystems) New PCR-RFLP methods were generated togenotype the SNP rs56245420 in the IL15 gene Primers 51015840-TTTCTGTTATTAACAAACATCACTCTG-31015840 and 51015840-CAACAC TTG TAC ATA TTT TTA TTC AAt AT-31015840 (mismatchis shown in bold lower case) were used for rs56245420 Otherfive SNPs were genotyped by PCR-RFLP methods describedpreviously with slight modification [11ndash15] PCR reactionwas carried out in a total volume of 20 120583L containing 20 ngof genomic DNA 1 times PCR buffer 15mMMgCl
2 200120583M
of each dNTP 30 ng of each primer and 1 unit of TaqDNA polymerase (TakaRa) Samples were denatured at 95∘Cfor 2min followed by 30 cycles of 94∘C for 45 sec 61∘C(rs2395029) or 54∘C (rs56245420) for 45 sec and 72∘C for45 sec and endedwith a final extension for 7min at 72∘C PCRproducts were digested with 4U of appropriate restrictionendonuclease and electrophoresed on 3 agarose gels andstained with ethidium bromide The restriction endonucle-ases PCR product lengths and restriction patterns are shownin Table 1
23 Data Analysis Statistics analysis was performed by SPSSsoftware for windows (SPSS Inc) The frequencies of geno-types and alleles for all the six studied loci were determinedassuming codominant inheritance The Hardy-Weinbergequilibrium (HWE) for six loci in psoriasis patients andcontrols was tested by means of chi-square tests The statis-tical significance of the genotype and allele frequency vari-ables between the psoriasis patients and control group wasevaluated by chi-square test with Yates correction for smallnumbers Relative risk associated with the significant geno-type was estimated by the odds ratio (OR) OR with 95confidence intervals (95 CI) was tested using a chi-squaredistribution and the null hypothesis being tested is OR = 1 119875values lt005 were considered as statistically significant
3 Results
Only one of the fourteen Hardy-Weinberg tests (seven poly-morphic loci each in the psoriasis patient and control groups)had 119875 values smaller than 005 (119875 = 001 at rs3212227in controls) All nine remaining genotype frequencies fitHardy-Weinberg expectations according to chi-square testsin psoriasis patients and controls (119875 gt 005) Therefore thereis no meaningful deviation from WHE and our populationis derived from random mating
Polymorphism (minor allele frequency gt 1) has beenfound for all studied SNPs except for rs11209026 in the IL23Rgene (Table 2) Table 2 shows that rs3212227 in the IL12B gene
4 International Journal of Genomics
Table 3 Correlation of psoriasis symptoms with SNPs in the IL genes
SNP Genotype Psoriasis Controls OR (95 CI) Allele Psoriasis Controls OR (95 CI)
rs2243250
TT 127 189 T 315 476TC 61 98 093 (063ndash137) C 85 120 107 (078ndash146)CC 12 11 162 (069ndash378)
TC-CC 73 109 100 (069ndash145)
rs1800872
AA 93 138 A 272 399AC 86 123 104 (071ndash152) C 128 197 095 (072ndash125)CC 21 37 084 (046ndash153)
AC-CC 107 160 099 (069ndash142)
rs3212227
CC 19 51 C 142 230AC 104 128 218 (121ndash392) A 258 366 114 (088ndash148)AA 77 119 171 (096ndash317)
AC-AA 181 247 197 (112ndash345)
rs1800925
CC 140 222 C 332 516CT 52 72 115 (076ndash174) T 68 80 132 (093ndash186)TT 8 4 317 (094ndash1072)
CT-CC 60 76 125 (084ndash186)
rs20541
CC 100 146 C 280 418CT 80 126 093 (064ndash136) T 120 178 101 (077ndash133)TT 20 26 112 (059ndash212)
CT-TT 100 152 096 (067ndash137)
rs56245420
AA 78 139 A 253 413AT 97 135 128 (087ndash187) T 147 183 128 (100ndash171)TT 25 24 185 (099ndash346)
AT-TT 122 159 136 (094ndash196)
(119875 = 00218) was associated with psoriasis at genotypic levelin the studied population Other SNPs examined were notassociated with psoriasis considered from single locus Asshown in Table 3 while the AC genotype (OR = 148 95CI 095ndash230) and the alleles (OR = 084 95 CI 063ndash113)at rs3212227 in the IL12B were not a risk factor of psoriasisthe CC genotype was a protective factor of psoriasis (OR =051 95 CI 027ndash096)
4 Discussion
The etiology of psoriasis is a complex interaction of envi-ronmental and biological factors Genetic factors may playa significant role in the risk of psoriasis in Chinese [10 16]Recent genetic studies indicate that the location of these genesvaries considerably among populations and families We areinterested to know if psoriasis is associatedwith the genes thathave been strongly associated with psoriasis in Europeans butnot well studied in Chinese
Our results showed that the IL12B gene was associatedwith psoriasis in Chinese at genotypic level (119875 lt 005) whichis in line with the findings from European studies [17] TheCC genotype for rs3212227 in IL12B is a protective factor(OR = 051) from psoriasis Similar result from studying SNPrs6887695 in IL12B showed that the minor allele C was aprotective factor from psoriasis [5]
The nonsynonymous SNP in IL23R rs11209026 widelythought to be the primary psoriasis-associated SNP in IL23Rin Europeans was found not to be polymorphic in Chinesewhich is in agreementwith the findings of others [18]The lowfrequencies of variant in IL23R are accordingly of low risk forpsoriasis in ChineseWith single SNP analysis no associationis found between the psoriasis and the IL4 IL10 IL13 andIL15 genes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Thisworkwas supported byGrants from theNationalNaturalScience Foundation of China (81360457) and the NaturalScience Foundation of Yunnan Province (2012FB099)
References
[1] J E Gudjonsson and J T Elder ldquoPsoriasis epidemiologyrdquoClinics in Dermatology vol 25 no 6 pp 535ndash546 2007
[2] R Parisi D P Symmons C E Griffiths and D M AshcroftldquoGlobal epidemiology of psoriasis a systematic review of
International Journal of Genomics 5
incidence and prevalencerdquo Journal of Investigative Dermatologyvol 133 no 2 pp 377ndash385 2013
[3] R P Nair T Henseler S Jenisch et al ldquoEvidence for twopsoriasis susceptibility loci (HLA and 17q) and two novelcandidate regions (16q and 20p) by genome-wide scanrdquoHumanMolecular Genetics vol 6 no 8 pp 1349ndash1356 1997
[4] K C Duffin andG G Krueger ldquoGenetic variations in cytokinesand cytokine receptors associated with psoriasis found bygenome-wide associationrdquo Journal of Investigative Dermatologyvol 129 no 4 pp 827ndash833 2009
[5] Y Liu C Helms W Liao et al ldquoA genome-wide associationstudy of psoriasis and psoriatic arthritis identifies new diseaselocirdquo PLoS Genetics vol 4 no 3 2008
[6] R P Nair K C Duffin C Helms et al ldquoGenome-wide scanreveals association of psoriasiswith IL-23 andNF-120581BpathwaysrdquoNature Genetics vol 41 no 2 pp 199ndash204 2009
[7] F Capon M J Bijlmakers N Wolf et al ldquoIdentificationof ZNF313RNF114 as a novel psoriasis susceptibility generdquoHuman Molecular Genetics vol 17 no 13 pp 1938ndash1945 2008
[8] R L Smith S Eyre R BWarrenH S Young C EMGriffithsand J Worthington ldquoNo association between polymorphismsin the interleukin-15 gene and early-onset psoriasis in a UKcohort suggests heterogeneity for this susceptibility locus iden-tified in Chinese psoriasis patientsrdquo Journal of InvestigativeDermatology vol 128 no 12 pp 2904ndash2905 2008
[9] W Weger A Hofer P Wolf et al ldquoRole of the interleukin15 96516AgtT and IL15 96330CgtA gene polymorphisms incaucasian patients with chronic plaque psoriasisrdquo Journal ofDermatological Science vol 51 no 2 pp 147ndash149 2008
[10] X J Zhang K L Yan Z M Wang et al ldquoPolymorphismsin interleukin-15 gene on chromosome 4q312 are associatedwith psoriasis vulgaris in Chinese populationrdquo Journal ofInvestigative Dermatology vol 127 no 11 pp 2544ndash2551 2007
[11] E Tarazona-Santos and S A Tishkoff ldquoDivergent patterns oflinkage disequilibrium and haplotype structure across globalpopulations at the interleukin-13 (IL13) locusrdquo Genes andImmunity vol 6 no 1 pp 53ndash65 2005
[12] P E Graves M Kabesch M Halonen et al ldquoA cluster of seventightly linked polymorphisms in the IL-13 gene is associatedwith total serum IgE levels in three populations of whitechildrenrdquo Journal of Allergy and Clinical Immunology vol 105no 3 pp 506ndash513 2000
[13] T Kawashima E Noguchi T Arinami et al ldquoLinkage andassociation of an interleukin 4 gene polymorphism with atopicdermatitis in Japanese familiesrdquo Journal ofMedical Genetics vol35 no 6 pp 502ndash504 1998
[14] C C Mok J S Lanchbury D W Chan and C S LauldquoInterleukin-10 promoter polymorphisms in Southern Chinesepatients with systemic lupus erythematosusrdquo Arthritis andRheumatology vol 41 no 6 pp 1090ndash1095 1998
[15] A Alvarado-NavarroMMontoya-Buelna J FMunoz-Valle RI Lopez-Roa C Guillen-Vargas and M Fafutis-Morris ldquoThe31015840UTR 1188 AC polymorphism in the interleukin-12p40 gene(IL-12B) is associated with lepromatous leprosy in the West ofMexicordquo Immunology Letters vol 118 no 2 pp 148ndash151 2008
[16] F Long C Sun D Deng X Zhou X P Li and Y P ZhangldquoTNF-238A is associated with juvenile onset psoriasis inpatients of Han population in Southwest Chinardquo Journal ofDermatological Science vol 36 no 2 pp 109ndash111 2004
[17] F Capon S Semprini B Dallapiccola and G Novelli ldquoEvi-dence for interaction between psoriasis-susceptibility loci on
chromosomes 6p21 and 1q21rdquo The American Journal of HumanGenetics vol 65 no 6 pp 1798ndash1800 1999
[18] S I Davidson X Wu Y Liu et al ldquoAssociation of ERAP1but not IL23R with ankylosing spondylitis in a Han ChinesepopulationrdquoArthritis and Rheumatism vol 60 no 11 pp 3263ndash3268 2009
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anatomy Research International
PeptidesInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporation httpwwwhindawicom
International Journal of
Volume 2014
Zoology
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Molecular Biology International
GenomicsInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioinformaticsAdvances in
Marine BiologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Signal TransductionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Evolutionary BiologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Biochemistry Research International
ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Genetics Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Virolog y
Hindawi Publishing Corporationhttpwwwhindawicom
Nucleic AcidsJournal of
Volume 2014
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Enzyme Research
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
International Journal of
Microbiology
International Journal of Genomics 3
Table 2 Genotyping of seven studied SNPs in psoriasis patients (119899 = 200) and controls (119899 = 298)
SNP Gene Population Genotype () Minor allele ()
rs2243250 IL4TT TC CC C
Controls 189 (634) 98 (329) 11 (37) 120 (201)Psoriasis 127 (635) 61 (305) 12 (60) 85 (213)
rs1800872 IL10AA AC CC C
Controls 138 (463) 123 (413) 37 (124) 197 (331)Psoriasis 93 (465) 86 (430) 21 (105) 128 (320)
rs3212227 IL12BAA AC CC C
Controls 119 (399) 128 (430) 51 (171) 230 (386)Psoriasis 77 (385) 104 (520) 19 (95)lowasta 142 (355)
rs1800925 IL13CC CT TT T
Controls 222 (745) 72 (242) 4 (13) 80 (134)Psoriasis 140 (700) 52 (260) 8 (40) 68 (170)
rs20541 IL13CC CT TT T
Controls 146 (490) 126 (423) 26 (87) 178 (299)Psoriasis 100 (500) 80 (400) 20 (100) 120 (300)
rs56245420 IL15AA AT TT T
Controls 139 (466) 135 (453) 24 (81) 183 (307)Psoriasis 78 (390) 97 (485) 25 (125) 147 (368)
rs11209026 IL23RGG GA AA A
Controls 298 (100) 0 0 0Psoriasis 200 (100) 0 0 0
lowasta119875 = 00218
with approval of the institutional review boards of the Affil-iated Yanrsquoan Hospital of Kunming Medical College and theKunming Institute of Botany Informed consent was obtainedfrom each participant before inclusion in this study
22 Determination of Genotype Genomic DNAs were iso-lated from whole blood using regular phenolchloroformmethod The SNP rs11209026 in the IL23R gene was geno-typed by the TaqMan allelic discrimination method (AppliedBiosystems) New PCR-RFLP methods were generated togenotype the SNP rs56245420 in the IL15 gene Primers 51015840-TTTCTGTTATTAACAAACATCACTCTG-31015840 and 51015840-CAACAC TTG TAC ATA TTT TTA TTC AAt AT-31015840 (mismatchis shown in bold lower case) were used for rs56245420 Otherfive SNPs were genotyped by PCR-RFLP methods describedpreviously with slight modification [11ndash15] PCR reactionwas carried out in a total volume of 20 120583L containing 20 ngof genomic DNA 1 times PCR buffer 15mMMgCl
2 200120583M
of each dNTP 30 ng of each primer and 1 unit of TaqDNA polymerase (TakaRa) Samples were denatured at 95∘Cfor 2min followed by 30 cycles of 94∘C for 45 sec 61∘C(rs2395029) or 54∘C (rs56245420) for 45 sec and 72∘C for45 sec and endedwith a final extension for 7min at 72∘C PCRproducts were digested with 4U of appropriate restrictionendonuclease and electrophoresed on 3 agarose gels andstained with ethidium bromide The restriction endonucle-ases PCR product lengths and restriction patterns are shownin Table 1
23 Data Analysis Statistics analysis was performed by SPSSsoftware for windows (SPSS Inc) The frequencies of geno-types and alleles for all the six studied loci were determinedassuming codominant inheritance The Hardy-Weinbergequilibrium (HWE) for six loci in psoriasis patients andcontrols was tested by means of chi-square tests The statis-tical significance of the genotype and allele frequency vari-ables between the psoriasis patients and control group wasevaluated by chi-square test with Yates correction for smallnumbers Relative risk associated with the significant geno-type was estimated by the odds ratio (OR) OR with 95confidence intervals (95 CI) was tested using a chi-squaredistribution and the null hypothesis being tested is OR = 1 119875values lt005 were considered as statistically significant
3 Results
Only one of the fourteen Hardy-Weinberg tests (seven poly-morphic loci each in the psoriasis patient and control groups)had 119875 values smaller than 005 (119875 = 001 at rs3212227in controls) All nine remaining genotype frequencies fitHardy-Weinberg expectations according to chi-square testsin psoriasis patients and controls (119875 gt 005) Therefore thereis no meaningful deviation from WHE and our populationis derived from random mating
Polymorphism (minor allele frequency gt 1) has beenfound for all studied SNPs except for rs11209026 in the IL23Rgene (Table 2) Table 2 shows that rs3212227 in the IL12B gene
4 International Journal of Genomics
Table 3 Correlation of psoriasis symptoms with SNPs in the IL genes
SNP Genotype Psoriasis Controls OR (95 CI) Allele Psoriasis Controls OR (95 CI)
rs2243250
TT 127 189 T 315 476TC 61 98 093 (063ndash137) C 85 120 107 (078ndash146)CC 12 11 162 (069ndash378)
TC-CC 73 109 100 (069ndash145)
rs1800872
AA 93 138 A 272 399AC 86 123 104 (071ndash152) C 128 197 095 (072ndash125)CC 21 37 084 (046ndash153)
AC-CC 107 160 099 (069ndash142)
rs3212227
CC 19 51 C 142 230AC 104 128 218 (121ndash392) A 258 366 114 (088ndash148)AA 77 119 171 (096ndash317)
AC-AA 181 247 197 (112ndash345)
rs1800925
CC 140 222 C 332 516CT 52 72 115 (076ndash174) T 68 80 132 (093ndash186)TT 8 4 317 (094ndash1072)
CT-CC 60 76 125 (084ndash186)
rs20541
CC 100 146 C 280 418CT 80 126 093 (064ndash136) T 120 178 101 (077ndash133)TT 20 26 112 (059ndash212)
CT-TT 100 152 096 (067ndash137)
rs56245420
AA 78 139 A 253 413AT 97 135 128 (087ndash187) T 147 183 128 (100ndash171)TT 25 24 185 (099ndash346)
AT-TT 122 159 136 (094ndash196)
(119875 = 00218) was associated with psoriasis at genotypic levelin the studied population Other SNPs examined were notassociated with psoriasis considered from single locus Asshown in Table 3 while the AC genotype (OR = 148 95CI 095ndash230) and the alleles (OR = 084 95 CI 063ndash113)at rs3212227 in the IL12B were not a risk factor of psoriasisthe CC genotype was a protective factor of psoriasis (OR =051 95 CI 027ndash096)
4 Discussion
The etiology of psoriasis is a complex interaction of envi-ronmental and biological factors Genetic factors may playa significant role in the risk of psoriasis in Chinese [10 16]Recent genetic studies indicate that the location of these genesvaries considerably among populations and families We areinterested to know if psoriasis is associatedwith the genes thathave been strongly associated with psoriasis in Europeans butnot well studied in Chinese
Our results showed that the IL12B gene was associatedwith psoriasis in Chinese at genotypic level (119875 lt 005) whichis in line with the findings from European studies [17] TheCC genotype for rs3212227 in IL12B is a protective factor(OR = 051) from psoriasis Similar result from studying SNPrs6887695 in IL12B showed that the minor allele C was aprotective factor from psoriasis [5]
The nonsynonymous SNP in IL23R rs11209026 widelythought to be the primary psoriasis-associated SNP in IL23Rin Europeans was found not to be polymorphic in Chinesewhich is in agreementwith the findings of others [18]The lowfrequencies of variant in IL23R are accordingly of low risk forpsoriasis in ChineseWith single SNP analysis no associationis found between the psoriasis and the IL4 IL10 IL13 andIL15 genes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Thisworkwas supported byGrants from theNationalNaturalScience Foundation of China (81360457) and the NaturalScience Foundation of Yunnan Province (2012FB099)
References
[1] J E Gudjonsson and J T Elder ldquoPsoriasis epidemiologyrdquoClinics in Dermatology vol 25 no 6 pp 535ndash546 2007
[2] R Parisi D P Symmons C E Griffiths and D M AshcroftldquoGlobal epidemiology of psoriasis a systematic review of
International Journal of Genomics 5
incidence and prevalencerdquo Journal of Investigative Dermatologyvol 133 no 2 pp 377ndash385 2013
[3] R P Nair T Henseler S Jenisch et al ldquoEvidence for twopsoriasis susceptibility loci (HLA and 17q) and two novelcandidate regions (16q and 20p) by genome-wide scanrdquoHumanMolecular Genetics vol 6 no 8 pp 1349ndash1356 1997
[4] K C Duffin andG G Krueger ldquoGenetic variations in cytokinesand cytokine receptors associated with psoriasis found bygenome-wide associationrdquo Journal of Investigative Dermatologyvol 129 no 4 pp 827ndash833 2009
[5] Y Liu C Helms W Liao et al ldquoA genome-wide associationstudy of psoriasis and psoriatic arthritis identifies new diseaselocirdquo PLoS Genetics vol 4 no 3 2008
[6] R P Nair K C Duffin C Helms et al ldquoGenome-wide scanreveals association of psoriasiswith IL-23 andNF-120581BpathwaysrdquoNature Genetics vol 41 no 2 pp 199ndash204 2009
[7] F Capon M J Bijlmakers N Wolf et al ldquoIdentificationof ZNF313RNF114 as a novel psoriasis susceptibility generdquoHuman Molecular Genetics vol 17 no 13 pp 1938ndash1945 2008
[8] R L Smith S Eyre R BWarrenH S Young C EMGriffithsand J Worthington ldquoNo association between polymorphismsin the interleukin-15 gene and early-onset psoriasis in a UKcohort suggests heterogeneity for this susceptibility locus iden-tified in Chinese psoriasis patientsrdquo Journal of InvestigativeDermatology vol 128 no 12 pp 2904ndash2905 2008
[9] W Weger A Hofer P Wolf et al ldquoRole of the interleukin15 96516AgtT and IL15 96330CgtA gene polymorphisms incaucasian patients with chronic plaque psoriasisrdquo Journal ofDermatological Science vol 51 no 2 pp 147ndash149 2008
[10] X J Zhang K L Yan Z M Wang et al ldquoPolymorphismsin interleukin-15 gene on chromosome 4q312 are associatedwith psoriasis vulgaris in Chinese populationrdquo Journal ofInvestigative Dermatology vol 127 no 11 pp 2544ndash2551 2007
[11] E Tarazona-Santos and S A Tishkoff ldquoDivergent patterns oflinkage disequilibrium and haplotype structure across globalpopulations at the interleukin-13 (IL13) locusrdquo Genes andImmunity vol 6 no 1 pp 53ndash65 2005
[12] P E Graves M Kabesch M Halonen et al ldquoA cluster of seventightly linked polymorphisms in the IL-13 gene is associatedwith total serum IgE levels in three populations of whitechildrenrdquo Journal of Allergy and Clinical Immunology vol 105no 3 pp 506ndash513 2000
[13] T Kawashima E Noguchi T Arinami et al ldquoLinkage andassociation of an interleukin 4 gene polymorphism with atopicdermatitis in Japanese familiesrdquo Journal ofMedical Genetics vol35 no 6 pp 502ndash504 1998
[14] C C Mok J S Lanchbury D W Chan and C S LauldquoInterleukin-10 promoter polymorphisms in Southern Chinesepatients with systemic lupus erythematosusrdquo Arthritis andRheumatology vol 41 no 6 pp 1090ndash1095 1998
[15] A Alvarado-NavarroMMontoya-Buelna J FMunoz-Valle RI Lopez-Roa C Guillen-Vargas and M Fafutis-Morris ldquoThe31015840UTR 1188 AC polymorphism in the interleukin-12p40 gene(IL-12B) is associated with lepromatous leprosy in the West ofMexicordquo Immunology Letters vol 118 no 2 pp 148ndash151 2008
[16] F Long C Sun D Deng X Zhou X P Li and Y P ZhangldquoTNF-238A is associated with juvenile onset psoriasis inpatients of Han population in Southwest Chinardquo Journal ofDermatological Science vol 36 no 2 pp 109ndash111 2004
[17] F Capon S Semprini B Dallapiccola and G Novelli ldquoEvi-dence for interaction between psoriasis-susceptibility loci on
chromosomes 6p21 and 1q21rdquo The American Journal of HumanGenetics vol 65 no 6 pp 1798ndash1800 1999
[18] S I Davidson X Wu Y Liu et al ldquoAssociation of ERAP1but not IL23R with ankylosing spondylitis in a Han ChinesepopulationrdquoArthritis and Rheumatism vol 60 no 11 pp 3263ndash3268 2009
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anatomy Research International
PeptidesInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporation httpwwwhindawicom
International Journal of
Volume 2014
Zoology
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Molecular Biology International
GenomicsInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioinformaticsAdvances in
Marine BiologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Signal TransductionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Evolutionary BiologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Biochemistry Research International
ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Genetics Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Virolog y
Hindawi Publishing Corporationhttpwwwhindawicom
Nucleic AcidsJournal of
Volume 2014
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Enzyme Research
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
International Journal of
Microbiology
4 International Journal of Genomics
Table 3 Correlation of psoriasis symptoms with SNPs in the IL genes
SNP Genotype Psoriasis Controls OR (95 CI) Allele Psoriasis Controls OR (95 CI)
rs2243250
TT 127 189 T 315 476TC 61 98 093 (063ndash137) C 85 120 107 (078ndash146)CC 12 11 162 (069ndash378)
TC-CC 73 109 100 (069ndash145)
rs1800872
AA 93 138 A 272 399AC 86 123 104 (071ndash152) C 128 197 095 (072ndash125)CC 21 37 084 (046ndash153)
AC-CC 107 160 099 (069ndash142)
rs3212227
CC 19 51 C 142 230AC 104 128 218 (121ndash392) A 258 366 114 (088ndash148)AA 77 119 171 (096ndash317)
AC-AA 181 247 197 (112ndash345)
rs1800925
CC 140 222 C 332 516CT 52 72 115 (076ndash174) T 68 80 132 (093ndash186)TT 8 4 317 (094ndash1072)
CT-CC 60 76 125 (084ndash186)
rs20541
CC 100 146 C 280 418CT 80 126 093 (064ndash136) T 120 178 101 (077ndash133)TT 20 26 112 (059ndash212)
CT-TT 100 152 096 (067ndash137)
rs56245420
AA 78 139 A 253 413AT 97 135 128 (087ndash187) T 147 183 128 (100ndash171)TT 25 24 185 (099ndash346)
AT-TT 122 159 136 (094ndash196)
(119875 = 00218) was associated with psoriasis at genotypic levelin the studied population Other SNPs examined were notassociated with psoriasis considered from single locus Asshown in Table 3 while the AC genotype (OR = 148 95CI 095ndash230) and the alleles (OR = 084 95 CI 063ndash113)at rs3212227 in the IL12B were not a risk factor of psoriasisthe CC genotype was a protective factor of psoriasis (OR =051 95 CI 027ndash096)
4 Discussion
The etiology of psoriasis is a complex interaction of envi-ronmental and biological factors Genetic factors may playa significant role in the risk of psoriasis in Chinese [10 16]Recent genetic studies indicate that the location of these genesvaries considerably among populations and families We areinterested to know if psoriasis is associatedwith the genes thathave been strongly associated with psoriasis in Europeans butnot well studied in Chinese
Our results showed that the IL12B gene was associatedwith psoriasis in Chinese at genotypic level (119875 lt 005) whichis in line with the findings from European studies [17] TheCC genotype for rs3212227 in IL12B is a protective factor(OR = 051) from psoriasis Similar result from studying SNPrs6887695 in IL12B showed that the minor allele C was aprotective factor from psoriasis [5]
The nonsynonymous SNP in IL23R rs11209026 widelythought to be the primary psoriasis-associated SNP in IL23Rin Europeans was found not to be polymorphic in Chinesewhich is in agreementwith the findings of others [18]The lowfrequencies of variant in IL23R are accordingly of low risk forpsoriasis in ChineseWith single SNP analysis no associationis found between the psoriasis and the IL4 IL10 IL13 andIL15 genes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Thisworkwas supported byGrants from theNationalNaturalScience Foundation of China (81360457) and the NaturalScience Foundation of Yunnan Province (2012FB099)
References
[1] J E Gudjonsson and J T Elder ldquoPsoriasis epidemiologyrdquoClinics in Dermatology vol 25 no 6 pp 535ndash546 2007
[2] R Parisi D P Symmons C E Griffiths and D M AshcroftldquoGlobal epidemiology of psoriasis a systematic review of
International Journal of Genomics 5
incidence and prevalencerdquo Journal of Investigative Dermatologyvol 133 no 2 pp 377ndash385 2013
[3] R P Nair T Henseler S Jenisch et al ldquoEvidence for twopsoriasis susceptibility loci (HLA and 17q) and two novelcandidate regions (16q and 20p) by genome-wide scanrdquoHumanMolecular Genetics vol 6 no 8 pp 1349ndash1356 1997
[4] K C Duffin andG G Krueger ldquoGenetic variations in cytokinesand cytokine receptors associated with psoriasis found bygenome-wide associationrdquo Journal of Investigative Dermatologyvol 129 no 4 pp 827ndash833 2009
[5] Y Liu C Helms W Liao et al ldquoA genome-wide associationstudy of psoriasis and psoriatic arthritis identifies new diseaselocirdquo PLoS Genetics vol 4 no 3 2008
[6] R P Nair K C Duffin C Helms et al ldquoGenome-wide scanreveals association of psoriasiswith IL-23 andNF-120581BpathwaysrdquoNature Genetics vol 41 no 2 pp 199ndash204 2009
[7] F Capon M J Bijlmakers N Wolf et al ldquoIdentificationof ZNF313RNF114 as a novel psoriasis susceptibility generdquoHuman Molecular Genetics vol 17 no 13 pp 1938ndash1945 2008
[8] R L Smith S Eyre R BWarrenH S Young C EMGriffithsand J Worthington ldquoNo association between polymorphismsin the interleukin-15 gene and early-onset psoriasis in a UKcohort suggests heterogeneity for this susceptibility locus iden-tified in Chinese psoriasis patientsrdquo Journal of InvestigativeDermatology vol 128 no 12 pp 2904ndash2905 2008
[9] W Weger A Hofer P Wolf et al ldquoRole of the interleukin15 96516AgtT and IL15 96330CgtA gene polymorphisms incaucasian patients with chronic plaque psoriasisrdquo Journal ofDermatological Science vol 51 no 2 pp 147ndash149 2008
[10] X J Zhang K L Yan Z M Wang et al ldquoPolymorphismsin interleukin-15 gene on chromosome 4q312 are associatedwith psoriasis vulgaris in Chinese populationrdquo Journal ofInvestigative Dermatology vol 127 no 11 pp 2544ndash2551 2007
[11] E Tarazona-Santos and S A Tishkoff ldquoDivergent patterns oflinkage disequilibrium and haplotype structure across globalpopulations at the interleukin-13 (IL13) locusrdquo Genes andImmunity vol 6 no 1 pp 53ndash65 2005
[12] P E Graves M Kabesch M Halonen et al ldquoA cluster of seventightly linked polymorphisms in the IL-13 gene is associatedwith total serum IgE levels in three populations of whitechildrenrdquo Journal of Allergy and Clinical Immunology vol 105no 3 pp 506ndash513 2000
[13] T Kawashima E Noguchi T Arinami et al ldquoLinkage andassociation of an interleukin 4 gene polymorphism with atopicdermatitis in Japanese familiesrdquo Journal ofMedical Genetics vol35 no 6 pp 502ndash504 1998
[14] C C Mok J S Lanchbury D W Chan and C S LauldquoInterleukin-10 promoter polymorphisms in Southern Chinesepatients with systemic lupus erythematosusrdquo Arthritis andRheumatology vol 41 no 6 pp 1090ndash1095 1998
[15] A Alvarado-NavarroMMontoya-Buelna J FMunoz-Valle RI Lopez-Roa C Guillen-Vargas and M Fafutis-Morris ldquoThe31015840UTR 1188 AC polymorphism in the interleukin-12p40 gene(IL-12B) is associated with lepromatous leprosy in the West ofMexicordquo Immunology Letters vol 118 no 2 pp 148ndash151 2008
[16] F Long C Sun D Deng X Zhou X P Li and Y P ZhangldquoTNF-238A is associated with juvenile onset psoriasis inpatients of Han population in Southwest Chinardquo Journal ofDermatological Science vol 36 no 2 pp 109ndash111 2004
[17] F Capon S Semprini B Dallapiccola and G Novelli ldquoEvi-dence for interaction between psoriasis-susceptibility loci on
chromosomes 6p21 and 1q21rdquo The American Journal of HumanGenetics vol 65 no 6 pp 1798ndash1800 1999
[18] S I Davidson X Wu Y Liu et al ldquoAssociation of ERAP1but not IL23R with ankylosing spondylitis in a Han ChinesepopulationrdquoArthritis and Rheumatism vol 60 no 11 pp 3263ndash3268 2009
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anatomy Research International
PeptidesInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporation httpwwwhindawicom
International Journal of
Volume 2014
Zoology
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Molecular Biology International
GenomicsInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioinformaticsAdvances in
Marine BiologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Signal TransductionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Evolutionary BiologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Biochemistry Research International
ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Genetics Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Virolog y
Hindawi Publishing Corporationhttpwwwhindawicom
Nucleic AcidsJournal of
Volume 2014
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Enzyme Research
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
International Journal of
Microbiology
International Journal of Genomics 5
incidence and prevalencerdquo Journal of Investigative Dermatologyvol 133 no 2 pp 377ndash385 2013
[3] R P Nair T Henseler S Jenisch et al ldquoEvidence for twopsoriasis susceptibility loci (HLA and 17q) and two novelcandidate regions (16q and 20p) by genome-wide scanrdquoHumanMolecular Genetics vol 6 no 8 pp 1349ndash1356 1997
[4] K C Duffin andG G Krueger ldquoGenetic variations in cytokinesand cytokine receptors associated with psoriasis found bygenome-wide associationrdquo Journal of Investigative Dermatologyvol 129 no 4 pp 827ndash833 2009
[5] Y Liu C Helms W Liao et al ldquoA genome-wide associationstudy of psoriasis and psoriatic arthritis identifies new diseaselocirdquo PLoS Genetics vol 4 no 3 2008
[6] R P Nair K C Duffin C Helms et al ldquoGenome-wide scanreveals association of psoriasiswith IL-23 andNF-120581BpathwaysrdquoNature Genetics vol 41 no 2 pp 199ndash204 2009
[7] F Capon M J Bijlmakers N Wolf et al ldquoIdentificationof ZNF313RNF114 as a novel psoriasis susceptibility generdquoHuman Molecular Genetics vol 17 no 13 pp 1938ndash1945 2008
[8] R L Smith S Eyre R BWarrenH S Young C EMGriffithsand J Worthington ldquoNo association between polymorphismsin the interleukin-15 gene and early-onset psoriasis in a UKcohort suggests heterogeneity for this susceptibility locus iden-tified in Chinese psoriasis patientsrdquo Journal of InvestigativeDermatology vol 128 no 12 pp 2904ndash2905 2008
[9] W Weger A Hofer P Wolf et al ldquoRole of the interleukin15 96516AgtT and IL15 96330CgtA gene polymorphisms incaucasian patients with chronic plaque psoriasisrdquo Journal ofDermatological Science vol 51 no 2 pp 147ndash149 2008
[10] X J Zhang K L Yan Z M Wang et al ldquoPolymorphismsin interleukin-15 gene on chromosome 4q312 are associatedwith psoriasis vulgaris in Chinese populationrdquo Journal ofInvestigative Dermatology vol 127 no 11 pp 2544ndash2551 2007
[11] E Tarazona-Santos and S A Tishkoff ldquoDivergent patterns oflinkage disequilibrium and haplotype structure across globalpopulations at the interleukin-13 (IL13) locusrdquo Genes andImmunity vol 6 no 1 pp 53ndash65 2005
[12] P E Graves M Kabesch M Halonen et al ldquoA cluster of seventightly linked polymorphisms in the IL-13 gene is associatedwith total serum IgE levels in three populations of whitechildrenrdquo Journal of Allergy and Clinical Immunology vol 105no 3 pp 506ndash513 2000
[13] T Kawashima E Noguchi T Arinami et al ldquoLinkage andassociation of an interleukin 4 gene polymorphism with atopicdermatitis in Japanese familiesrdquo Journal ofMedical Genetics vol35 no 6 pp 502ndash504 1998
[14] C C Mok J S Lanchbury D W Chan and C S LauldquoInterleukin-10 promoter polymorphisms in Southern Chinesepatients with systemic lupus erythematosusrdquo Arthritis andRheumatology vol 41 no 6 pp 1090ndash1095 1998
[15] A Alvarado-NavarroMMontoya-Buelna J FMunoz-Valle RI Lopez-Roa C Guillen-Vargas and M Fafutis-Morris ldquoThe31015840UTR 1188 AC polymorphism in the interleukin-12p40 gene(IL-12B) is associated with lepromatous leprosy in the West ofMexicordquo Immunology Letters vol 118 no 2 pp 148ndash151 2008
[16] F Long C Sun D Deng X Zhou X P Li and Y P ZhangldquoTNF-238A is associated with juvenile onset psoriasis inpatients of Han population in Southwest Chinardquo Journal ofDermatological Science vol 36 no 2 pp 109ndash111 2004
[17] F Capon S Semprini B Dallapiccola and G Novelli ldquoEvi-dence for interaction between psoriasis-susceptibility loci on
chromosomes 6p21 and 1q21rdquo The American Journal of HumanGenetics vol 65 no 6 pp 1798ndash1800 1999
[18] S I Davidson X Wu Y Liu et al ldquoAssociation of ERAP1but not IL23R with ankylosing spondylitis in a Han ChinesepopulationrdquoArthritis and Rheumatism vol 60 no 11 pp 3263ndash3268 2009
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anatomy Research International
PeptidesInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporation httpwwwhindawicom
International Journal of
Volume 2014
Zoology
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Molecular Biology International
GenomicsInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioinformaticsAdvances in
Marine BiologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Signal TransductionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Evolutionary BiologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Biochemistry Research International
ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Genetics Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Virolog y
Hindawi Publishing Corporationhttpwwwhindawicom
Nucleic AcidsJournal of
Volume 2014
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Enzyme Research
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
International Journal of
Microbiology
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anatomy Research International
PeptidesInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporation httpwwwhindawicom
International Journal of
Volume 2014
Zoology
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Molecular Biology International
GenomicsInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioinformaticsAdvances in
Marine BiologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Signal TransductionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Evolutionary BiologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Biochemistry Research International
ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Genetics Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Virolog y
Hindawi Publishing Corporationhttpwwwhindawicom
Nucleic AcidsJournal of
Volume 2014
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Enzyme Research
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
International Journal of
Microbiology