REVIEW

Cytokine gene polymorphism in human disease: on-linedatabases, Supplement 3

MV Hollegaard1,2,3 and JL Bidwell41NANEA at Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark; 2Department of ClinicalBiochemistry Statens Serum Institut, Copenhagen, Denmark; 3Department of Biochemistry and Molecular Biology, University ofSouthern Denmark, Odense, Denmark and 4Department of Pathology and Microbiology, University of Bristol, Homeopathic HospitalSite, Cotham, Bristol, UK

Within the past few years, the focus on cytokine single nucleotide polymorphism (SNP) function and association with humandiseases has increased considerably. This third supplement to the Cytokine Gene Polymorphism in Human Disease: On-linedatabase describes the positive associations of cytokine SNPs in human diseases described in articles published from 2002 upto 2005. A file containing a list of all SNPs investigated in this period of time and their association with human disease orexpression pattern can be downloaded from the internet address http://www.nanea.dk/cytokinesnps/. The web pages alsocontain other features and downloads that could be useful when planning cytokine SNP association studies.Genes and Immunity (2006) 7, 269276. doi:10.1038/sj.gene.6364301; published online 27 April 2006

Keywords: cytokine; SNP; polymorphism; variation; disease; expression

Introduction

The Cytokine Gene Polymorphism in Human Disease:on-line database was first published in Genes andImmunity in 1999.1 The first update, supplement 1, camein 20012 and supplement 2 in 2002.3 Supplement 3updates the database with articles from 2002 to early2005. As the number of articles investigating cytokinesingle nucleotide polymorphism (SNP)disease associa-tions has increased substantially in the past few yearsand as this supplement covers more than 1 year, we havechosen only to show the SNPs that have an associationwith a specific disease in Table 1. A full version ofsupplement 3 is available for download from the on-linedatabase at the new permanent web address www.nanea.dk/cytokinesnps/. This version includes links toPubMed as well as the SNPs that was not found to beassociated with a disease. A few changes have beenmade in this supplement compared to earlier issues, themost prominent one being that the data are presented ina Microsoft Excel spreadsheet, allowing the reader tosearch and sort the SNPs, authors and diseases. Withregard to naming of the SNPs, we have chosen to use theOMIM gene names (http://www.ncbi.nlm.nih.gov) andfurthermore, we have grouped those SNPs that havenumerous names under one name. For example, TNFA308 G4A is also known as TNF NcoI or TNF1/2: in this

new supplement, it is named TNF 307 G4A (308,TNF1/2, NcoI). We would like to encourage authorsof SNP studies to supply the readers with an SNP rsnumber and OMIM gene names.

Not all genes in the supplement are cytokines, butthose that are not, are included because they wereinvestigated in the same study as the cytokine genes. Weare aware that some articles could be absent in this andprevious supplement updates as we have chosen to usePubMed as our primary article source and have stringentsearch criteria. Furthermore, we have excluded manu-scripts if they were difficult to obtain, not written inEnglish or it was not clear which SNPs were investi-gated. To correct, add or change interpreted data insupplement 3, we encourage authors to contact thecorresponding author. Besides the association studies,the new website also contains an Excel spreadsheetcontaining the in vivo/vitro studies.

The web pages have been redesigned to amalgamateall data from the previously published initial review, twoprevious supplements and the present supplement. Anew feature is the Links Navigator page, which provideslinks to: the CHIP Bioinformatics SNP per entries foreach gene (http://snpper.chip.org/);4 the appropriategene in the UCSC Genome Bioinformatics site (http://genome.cse.ucsc.edu/);5 the appropriate intra-site entrieson the polymorphism, expression and disease associa-tion pages (see navigation bar to the left of the mainwindow in Figure 1) and finally to annotated nucleotidesequence alignments where available. In the LinksNavigator, genes have been grouped into five classes:TNF superfamily ligands and receptors; interleukinligands/antagonists and interleukin receptors andother cytokines/growth factors/receptors. The data

Received 2 March 2006; accepted 9 March 2006; published online 27April 2006

Correspondence: MV Hollegaard, Department of Clinical Bio-chemistry, Statens Serum Institut, Artillerivej 5, Copenhagen 2300,Denmark.E-mail: mvh@ssi.dk

Genes and Immunity (2006) 7, 269276& 2006 Nature Publishing Group All rights reserved 1466-4879/06 $30.00

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Table 1 In vivo disease-association studies

Disease Yes

Acute appendicitis IL6 174 C4GAcute lung injury PBEF 1001 T4G, PBEF 1543 C4TAcute lymphoblastic leukemia IL10 1117 T4C, TNF 307 G4AAcute rejection IL10 854 T4C, IL10 haplotypes, IL2 n repeat, TNF 307 G4AAcute renal failure IL10 1117 T4C, TNF 307 G4AAcute resistance exercise IL1A +4845 G4T, IL1B +3953 C4T, IL1B 3737, IL1B 511 C4T, IL1RN +2018 T4CAggressive lymphoma IL10 1117 T4CAggressive periodontitis IL1B +3953 C4TAIDS IL4 IL10 haplotypes, 64 SNPs, IL10 627 C4A, IFNG 179 T4GAlcoholism IL6 174 C4GAllergic asthma IL4R +148 A4G, IL4R +1902 G4T, IL13 +2044, IL1A +4845 G4T, IL1B 511 C4T, IL1RN 86 bp VNTR,

TGFB1 869 C4T, TGFB1 915 G4C, TNF 307 G4AAllergic contact dermatitis TNF 307 G4AAllograft function IFNG +874 A4T, IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL2 330 T4G, IL6 174 C4G,

TGFB1 869 C4T, TGFB1 915 G4C, TNF 307 G4AAlopecia areata IL1-L1+4734, IL1RN +2018 T4C, IL1RN 86 bp VNTRAlopecia totalis alopeciauniversalis

IL13 +2044, IL13 1111 C4T, IL4 590 C4T, IL4R +148 A4G, IL4R +1682 T4C, IL4R +1902 G4T

Alzheimer disease IL10 1117 T4C, IL6 174 C4G, IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL1A 889 C4T,IL1B +3953 C4T, IL1B 511 C4T, IL1RN 86 bp VNTR, IL6 174 C4G, IL6 30UTR VNTR, TNF 1032T4C, TNF 857 C4T, TNF 863 C4A

Amyloid A amyloidosis IL1B 511 C4TAngiotensin-converting enzyme PAI1 675 4G45GAnkylosing spondylitis IL1RN 30735 T4C, IL1RN 31017 G4C, IL1RN 86 bp VNTRAsthma IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL12B +4237 G4A, IL12B +6402 A4C, IL12B

promoter, IL15 +10504 A4G, IL15 +13687 C4A, IL15 +14035 A4T, IL15 +267 C4T, IL15 +367 G4A, IL18137 G4C, IL1B 511 C4T, IL3 +79 T4C, IL4 33 C4T, IL4 590 C4T, IL4 int3 70 bp VNTR, IL4R+1902 G4T, IL8 251 T4A, TLR4 +896 A4G, TNF 1032 T4C, TNF 307 G4A, TNF 857 C4T, TNF863 C4A

Atherogenesis TLR4 +896 A4GAtherosclerosis IL6 174 C4GAtopic asthma CCL5 403 G4A, haplotypes TNF24DRB1*03 TNF24*B1*1104, IL4R +148 A4G, IL4R +1902 G4T,

IL4R 3223 C4T, TNF 307 G4A, IL12B 1188 A4C, IL13 +2044, IL13 +4257 G4A, IL13 1111 C4T,IL4 590 C4T, IL4R +148 A4G, IL4R 3223 C4T

Atopic eczema IL4R +1902 G4TAtopic rhinitis IL4R 1432 T4CAtopy IL13 +2044, IL18 137 G4C, IL18 607 C4A, IL1A +4845 G4T, IL1RN 86 bp VNTR, IL4R +1902 G4TAtrial fibrillation IL6 174 C4GAtrophic gastritis IL1B 31 T4CAttention-deficit4hyperactivitydisorder

IL1RN 86 bp VNTR

AV fistula patency TGFB1 869 C4T, TGFB1 915 G4CBasal cell carcinoma MTHFR +677 C4TBehcets disease TNF 1032 T4C, TNF 237 G4A, IL1A 889 C4T, IL1B +3953 C4TBe-hypersensitivity TNF 307 G4A, TNF 857 C4TBipolar I disorder TNF 307 G4ABladder cancer IL4 int3 70 bp VNTR, TNF 307 G4A, VEGF 2578 C4ABladder tumors TNF 307 G4ABlood pressure IL1B 511 C4T, TNF 307 G4ABody mass index IL6 174 C4G, IL6 CA repeat, TNF 307 G4ABone marrow transplantation IL1A 889 C4T, IL1B 511 C4T, TGFB1 869 C4T, TGFB1TII 1167 C4T, TNF 1032 T4C, TNF 857

C4T, TNF 863 C4A, TNFRSF1B +676 G4TBone mineral density CCR2 +190 G4A, IL10 627 C4A, IL1RN 86 bp VNTR, IL6 174 C4G, IL6 572 G4C, IL6 634 C4G,

IL6 CA repeat, LTA +252 A4G, OPG 209 G4A, OPG 245 T4G, OPG A163G, PLOD1 +84 G4A, PLOD11097 G4A, PLOD1 1406 T4C, PLOD1 1734 C4T, PLOD1 1832 A4C, PLOD1 1988 G4T, PLOD1 2324T4C, PLOD1 2333 C4G, PLOD1 494 C4T , PLOD1 495 G4A, PLOD1 G-86A, PLOD1 T-17G, TNF 1032T4C, TNF 307 G4A, TNF 857 C4T, TNF 863 C4A, TNFRSF1B +1663 G4A, TNFRSF1B +1668T4G, TNFRSF1B +1690 T4C, TNFRSF1B +593 G4A, TNFRSF1B +598 T4G, TNFRSF1B +620 T4C,TNFRSF1B +676 G4T, VDR 2 C4T

Brain arteriovenousmalformation

IL6 174 C4G

Breast cancer IL6 174 C4GBronchial asthma IL5 703 C4TBronchopulmonary dysplasia TNF 307 G4AC. pneumoniae infection CD14 260 C4TCalcific aortic stenosis IL10 1117 T4C, IL10 627 C4A, IL10 854 T4CCardiac surgery TNF 307 G4ACardiovascular disease IL10 1117 T4C, IL6 174 C4G, TGFB1 915 G4CCarotid atherosclerosis IL1RN 86 bp VNTRCarotid intimal-medial wallthickness

IL6 174 C4G

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Table 1 Continued

Disease Yes

Carotid plaque IL6 174 C4GCeliac disease LTA +252 A4G, TNF 307 G4ACerebral infarction IL1A 889 C4T, IL1RN 86 bp VNTR, LTA +252 A4G, TNF 307 G4ACerebral injury IL6 174 C4GCerebral malaria TNF 1032 T4C, TNF 237 G4A, TNF 307 G4A, TNF 857 C4T, TNF 863 C4ACervical abormalities IL10 1117 T4CCervical cancer IFNA +551 T4G, IL1RN 86 bp VNTR, TNF 237 G4A, TNF 375 G4A, TNF 572 A4C, TNF 857

C4T, TNF 863 C4ACervical intra-epithelial neoplasia TNF 307 G4AChlamydia trachomatis IL10 1117 T4CChorioamnionitis TNF 307 G4AChronic alcoholic liver disease IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL10.G microsat., LTA +252 A4GChronic allograft nelphropathy IL6 174 C4G, MTHFR +677 C4TChronic atrophic gastritis/gastriccarcinoma

IL1B 511 C4T, IL1RN 86 bp VNTR, TNF 307 G4A

Chronic hepatitis B IFNG +874 A4TChronic hepatitis B virusinfection

LTA +252 A4G, TNF 307 G4A

Chronic hepatitis C IL1B 511 C4T, TNF 237 G4AChronic hepatitis C virus IL10 1117 T4C, TGFB1 869 C4T, LTA +252 A4GChronic immunethrombocytopenic purpura

LTA +252 A4G

Chronic lung tuberculosis IL10 1117 T4C, TNF 307 G4AChronic obstructive pulmonarydisease

IL10 1117 T4C, TGFB1 869 C4T, LTA +252 A4G

Chronic pelvic pain syndrome IL10 1117 T4CChronic periodontitis LTA +252 A4G, TNF 307 G4A, IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL2 330 T4G,

IL6 174 C4G, IL6 572 G4C, TGFB1 509 C4T, TNFRSF1B +587 T4G, VDR +352 T4CChronic rejection IL10 1117 T4C, IL1RN 86 bp VNTR, IL4 33 C4TChronic schizophrenia TNF 307 G4ACoal workers pneumoconiosis TNF 307 G4ACoeliac disease TNF 307 G4AColorectal cancer IL6 174 C4G, IL8 251 T4A, PPARG C4GCommunity acquired pneumonia IL10 1117 T4CCongenital heart block/neonatallupus

TGFB1 869 C4T, TGFB1 915 G4C, TNF 307 G4A

Contact allergy IL16 295 T4CContact hypersensitivity TNF 1032 T4C, TNF 863 C4A, TNFd microsat.,COPD IL4 33 C4T, IL4 590 C4T, IL4 int3 70 bp VNTRCoronary artery bypass grafting LTA +252 A4G, TNF 307 G4ACoronary artery disease CX37 1019C4T, IL6 174 C4G, MMP3 1171 5A46A, TNF 863 C4ACoronary artery stenosis PECAM1 R643GCoronary atherosclerosis IL1RN 86 bp VNTRCoronary function IL1B 511 C4TCoronary heart disease IL10 1117 T4C, IL6 174 C4G, TNF 307 G4ACortical bone resorption IL6 174 C4GCrohns disease TNFRSF1B +1466 A4G, TNFRSF1B +1493 C4T, IL16 295 T4C, IL18 +105 A4C, TNF 863 C4ACutaneous malignant melanoma TNF 237 G4A, VEGF +405 G4C, VEGF +936 C4T, VEGF 1154 G4A, VEGF 2578 C4ACutaneous neonatal lupus TNF 307 G4ACutaneous T-cell lymphoma IL6 599 A4GDementia TNF 307 G4A, TNF 850 C4TDengue fever TNF 307 G4A, VDR +352 T4CDermatomyositis TNF 307 G4ADiabetic nephropathy CCL5 28 C4G, IL1B 511 C4T, IL1RN 86 bp VNTR, IL6 634 C4GDiarrhea IL8 251 T4ADiscoid rash IL4 590 C4T, IL4 int3 70 bp VNTRDistal gastric cancer IL1B 31 T4CDuodenal ulcers IL1B +3953 C4T, IL1B 31 T4C, IL1B 511 C4T, IL1RN 86 bp VNTR, IL8 251 T4AEarly-onset joint erosions inpsoriatic arthritis

LTA +252 A4G, TNF 307 G4A

Early-onset periodontitis IL1RN 86 bp VNTREclampsia TNF 307 G4AEnd-stage non-ischemicmyocardial dysfunction

TNF 307 G4A

Endemic pemphigus foliaceus IL4 590 C4T, IL6 174 C4GEndometriosis IFNG intron 1 CA rep., IL10 627 C4A, TNF 1032 T4C, TNF 857 C4T, TNF 863 C4AEnd-stage renal disease CTLA4 318 C4T, IFNG +874 A4T, IL10 GCC4ACC promotor genotype, IL1RN 120 T4C, long CTLA4

ATn repeatsFamilial RA TNFRSF1B +676 G4TFasting glycemia lipid parameters LTA +252 A4G, IL10.G microsat.Fat-free mass IL6 174 C4G

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Table 1 Continued

Disease Yes

Febrile convulsion IL1RN 86 bp VNTRFebrile seizures IL1B 511 C4TFocal segmentalglomerulosclerosis

IL10 1117 T4C

Fulminant hepatitis TNF 1032 T4C, TNF 863 C4AGastric adenocarcinoma IL1B 31 T4C, iNOS CCTTT pentanucleotideGastric cancer IL10 1117 T4C, IL1B 1473 C4G, IL1B 31 T4C, IL1B 511 C4T, IL1RN 86 bp VNTR, IL8 251 T4A,

LTA +252 A4G, LTA +804 C4A, MMP1 1607 G del., TNF 1032 T4C, TNF 237 G4A, TNF 307G4A, TNF 857 C4T, TNF 863 C4A

Gastric carcinoma IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL1B 511 C4T, IL1RN 86 bp VNTRGastric diseases IL8 251 T4AGastric inflammation IL1B +231, IL1B 511 C4T, IL1RN 86 bp VNTRGastric mucosa-associatedlymphoid tissue lymphoma

TNF 857 C4T, IL1B 31 T4C, IL1RN 86 bp VNTR

Gastroesophageal reflux disease IL1B 31 T4C, IL1B 511 C4T, IL1RN 86 bp VNTRGeneralized aggressiveperiodontitis

IL1A +4845 G4T, IL1B +3953 C4T, IL1B 511 C4T, IL1RN 86 bp VNTR

Glaucoma TNF 307 G4A, TNF 857 C4T, TNF 863 C4AGlucose tolerance IL6 174 C4GGlucose-6-phosphatedehydrogenase deficiency

IFNG +874 A4T, IL10 627 C4A, IL6 174 C4G

Graft-versus-host disease IL10 627 C4A, TNFRSF1B +676 G4T, IL2 330 T4G, IL1A 46 bp VNTR, IL1A 889 C4T, IFNG +874A4T, IL10 1117 T4C, IL10 854 T4C, IL1B +3953 C4T, IL6 174 C4G, TNF +488 G4A, TNFdmicrosat.

Graves disease IL13 +2044, IL13 1111 C4T, LTA +252 A4G, TNF 237 G4A, TNF 307 G4AHematological malignancies:toxic complications

LTA +252 A4G, TNF 307 G4A

Hashimoto thyroiditis TNF 307 G4AHayfever/atopy IL2 330 T4G, IL6 174 C4GHCV infection IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL6 174 C4GHCV viral clearance IL6 174 C4G, TGFB1 869 C4T, TGFB1 915 G4CHCV-induced cirrhosis IL1B 511 C4T, IL1RN 86 bp VNTRHeart rate IL6 599 A4GHelicobacter pylori infection IL10 854 T4C, IL1B 511 C4T, IL8 251 T4AHelicobacter pylori seropositivity IL1B 31 T4CHelicobacter pylori-associateddiseases

IL1R1 1622 A4G, IFNG +874 A4T, IL10 854 T4C, TNF 857 C4T

Henoch-Schonlein purpura TGFB1 509 C4THepatitis B vaccination IL12B promoter, IL1B +3953 C4T, IL2 330 T4G, IL4 1098 T4G, IL4 33 C4T, IL4 590 C4THepatitis B virus IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, TNF 1032 T4C, TNF 161 G4A, TNF 237 G4A,

TNF 375 G4A, TNF 307 G4A, TNF 857 C4T, TNF 863 C4AHepatitis C virus IL10 1117 T4C, OPN 443 T4C, TNF 307 G4A, TNF 863 C4AHepatitis C virus infection TNF +1304 A4G, TNF +851 A4G, TNF 1032 T4C, TNF 1073 C4T, TNF 237 G4A, TNF 243

G4A, TNF 307 G4A, TNF 375 G4A, TNF 863 C4AHepatocellular carcinoma IFNG +874 A4T, IL10 1117 T4C, IL10 854 T4C, IL12B 1188 A4C, IL18 137 G4C, IL1RN 86 bp

VNTR, IL2 330 T4G, IL4 590 C4T, IL6 174 C4G, TNF 307 G4AHerpes zoster IL10 1117 T4C, IL10 627 C4A, IL10 854 T4CHIV IL4 590 C4THIV rel. lipodystrophy TNF 237 G4A, TNF 307 G4AHIV replication IL1A 889 C4THIV: immune restoration disease IL12B 1188 A4C, IL6 174 C4G, TNF 307 G4AHIV-1 infection IL10 627 C4A, IL4 590 C4T, TNF 307 G4AHIV-1 viremia TNF 1032 T4C, TNF 863 C4AHodgkin lymphoma IL6 174 C4G, TNFa microsat.HTLV-I-associatedmyelopathy4tropical spasticparaparesis

IL10 627 C4A

Hyperandrogenism IL6 174 C4G, IL6 599 A4GHypertension CCR2 +190 G4A, IL1B 31 T4C, TNF 237 G4AIdiopathic pulmonary fibrosis TNF 307 G4AIdiopathic recurrent miscarriage HO-1 GTn microsatellite sizeIgA nephropathy IFNG intron 1 CA rep., IL1B 511 C4T, IL1RN 86 bp VNTR, IL4 int3 70 bp VNTR, TGFB1 509 C4T,

TGFB1 869 C4T, TNF 307 G4A, IL10 1117 T4CIgE levels IL4R haplotype 50478, IL4R haplotype 50551Immunosuppressive therapy TNF 307 G4AInflammatory bowel disease ICAM1 K469E, IL18 +113 T4G, IL18 +127 C4T, IL1RN 86 bp VNTR, TNF 307 G4A, TNF 857 C4T,

TNFRSF1A +36 A4G, TNFRSF1B +587 T4GInflammatory stress: fish oil IL1B 511 C4T, IL6 174 C4G, LTA +252 A4G, TNF 307 G4AInsulin resistance TNF 307 G4A, PPARG C4GInsulin sensitivity IL6 174 C4G

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Table 1 Continued

Disease Yes

Intima-media thickness of thecarotid artery in hypertensivepatients

OPG 950 T4C

Ischemic stroke CRP +1059 G4C, ICAM1 K469E, IL1B 511 C4T, IL1RN 86 bp VNTR, IL6 174 C4G, MCP1 2518A4G, MIF 173 G4C, MMP3 1171 5A46A, TNF 307 G4A

Juvenile idiopathic arthritis IL13 R110Q, IL1B +3962 T4C, IL4 1098 T4G, IL6 174 C4G, MICA microsat., MIF 173 G4C, TNF307 G4A, TNFa microsat.

Juvenile oligoarthritis TNF +851 A4GKaposis sarcoma IL6 174 C4G, IL8 251 T4A, CD14 159 C4T, VEGF 634 C4GKidney allograft survival IL6 174 C4G, IL6 599 A4GKidney graft survival TNF 307 G4AKidney transplantation TNF 307 G4ALacunar infarction IL6 174 C4GLacunar stroke IL6 174 C4GLatent autoimmune diabetes inadults

TNF 307 G4A

Late-onset Alzheimer disease TNF 307 G4ALeiomyomas TNF 307 G4ALeishmania chagasi infection TNF 307 G4ALeprosy IL10 2763 C4A, IL10 2849 A4G, IL10 3575 T4ALipodystrophy TNF 237 G4ALiver transplants TNF 307 G4ALofgrens syndrome LTA +252 A4G, TNF 307 G4ALongevity IFNG +874 A4T, IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL6 174 C4G, TGFB1 915 G4C,

TNF 307 G4ALung cancer IL8 251 T4ALung junction IL10 +1668 A4TLupus nephritis IFNG intron 1 CA rep.Major depressive disorder IL1B 511 C4T, MCP1 2518 A4G, TNF 307 G4AMalaria IL12B 1188 A4C, IL12B promoter, IL1A +4845 G4T, IL1B +3953 C4T, IL4 int3 70 bp VNTR, iNOS 954

G4CMarginal bone loss IL1B 511 C4TMelanoma patients IFNG +874 A4T, IL10 1117 T4CMeningococcal disease IL10 1117 T4C, IL1B 511 C4T, IL1RN +2018 T4C, IL1RN 86 bp VNTR, IL6 174 C4GMicroscopic polyangiitis IL10 1117 T4CMigraine IL1A 889 C4T, LTA +252 A4G, TNF 307 G4AMixed connective tissue disease MICA microsat., TNF 307 G4AMortality in patients with severesepsis

IL1RN 86 bp VNTR

Multi-infarct dementia IL6 174 C4GMultiple organ dysfunctionsyndrome

IL10 627 C4A

Multiple sclerosis C1_3_2, C132*354, D6S265, D6S276, IFNG +5644 G4A, IFNG intron 1 CA rep., IL10 1117 T4C,IL10.G microsat., IL1A 889 C4T, IL1B +1903, IL1B +3876, IL1B +3953 C4T, IL1B 511 C4T, IL1RN86 bp VNTR, IL4 +2580 C4A, IL4 33 C4T, IL4 590 C4T, IL4 709 VNTR, LTA +252 A4G, MCP3 geneCA4GA microsatellite, OPN +8090 C4T, OPN +9583 G4A, TNF 307 G4A, TNF 375 G4A, TNFamicrosat., TNFRSF1B +1668 T4G

Multiple system atrophy IL1A 889 C4T, IL1B 511 C4T, IL8 251 T4A, TNF 1032 T4CMuscle hypertrophy IL15RA C4A exon 7Myasthenia gravis IL1A 889 C4TMyelodysplastic syndrome TNF 307 G4AMyelopathy IL6 634 C4GMyocardial infarction IL1B 511 C4T, IL6 174 C4G, PECAM1 G670R, PECAM1 N563S, PECAM1 R643G, TNFRSF1A R92QNarcolepsy TNF 857 C4TNasal polyposis IL1A +4845 G4TNasopharyngeal carcinoma HSP702 +1267Necrotizing enterocolitis IL4R +1902 G4TNeonatal morbidity IL1RN 86 bp VNTRNeonatal sepsis IL6 174 C4GNephropathy VEGF 2549 18 bp del4insNephrotic syndrome IL1RN 86 bp VNTRNon-alcoholic fatty liver TNF 237 G4ANon-alcoholic steatohepatitis IL1B 511 C4TNon-Hodgkins lymphoma TNF 307 G4ANonimmunologic post-transplantcomplications: diabetes

TGFB1 915 G4C, IL10 1117 T4C, IFNG +874 A4T

Obesity IL6 174 C4G, IL6R +3944 T4G, IL6R c_1158918_10, IL6R c_30046_10, IL6R rs1138004, IL6R rs1138006,TNF 307 G4A

Oesophagitis IL1B 511 C4T, IL1RN 86 bp VNTROral lichen planus IFNG +5644 G4A, TNF 307 G4AOral submucous fibrosis TNF 307 G4A

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Table 1 Continued

Disease Yes

Osseointegrated implants IL1A +4845 G4T, IL1B +3953 C4TOssification IL1B 511 C4TOsteoarthritis IL1A 889 C4T, IL1A IVS4 n rep., IL1B +3953 C4T, IL1B 31 T4C, IL1B 511 C4T, IL1B 5810 G4A,

IL1RN +11100 T4C, IL1RN +8006 T4C, IL1RN 86 bp VNTR, IL4R +1124 A4C, IL4R +1232 C4T, IL4R+148 A4G, IL4R +1682 T4C, IL4R +1902 G4T, IL4R +676 C4T, IL4R 1914, IL4R 3223 C4T, IL4RS727A

Osteolysis TNF 237 G4AOsteomyelitis IL1A 889 C4T, IL1B +3953 C4TOsteoporosis IL1B +3953 C4T, IL6 174 C4G, OPG 223 T4C, TNFRSF1B +593 A +598 T +620 C homozygous

haplotypeOvarian cancer IL1RN 86 bp VNTR, IL6 174 C4GOzone-induced change in lungfunction

LTA +252 A4G, TNF 1032 T4C, TNF 237 G4A, TNF 307 G4A, TNF 375 G4A

Parkinsons disease IL1B 511 C4T, IL6 174 C4G, IL8 251 T4AParoxysmal nocturnalhemoglobinuria aplastic anemia

IFNG +874 A4T, TGFB1 869 C4T, TGFB1 915 G4C

Patchy alopecia areata IL1RN 86 bp VNTRPemphigus foliaceus IL10 854 T4C, IL10 haplotype 10824819 A4T, TNF 307 G4APeri-implant bone loss IL1A +4845 G4T, IL1B +3953 C4TPeriodontal disease IL1A +4845 G4T, IL1A 889 C4T, IL1B +3953 C4T, IL1RN 86 bp VNTRPeriodontitis IL1A 889 C4T, IL1B +3953 C4T, IL1RN 86 bp VNTR, IL6 174 C4G, TNF 307 G4APeripheral artery occlusivedisease

IL6 174 C4G

Peritoneal adhesions IL1RN 86 bp VNTRPeyronies disease TGFB1 915 G4CPlacental inflammation LTA +252 A4G, TNF 237 G4APlasmodium falciparumreinfections

TNF 307 G4A

Pneumococcal septic shock IL10 1117 T4CPostoperative complications LTA +252 A4GPPROM Homozygosity for IL10 1082G4 819C4592C haplotypePR3-ANCA vasculitis IL1B +3953 C4T, IL1RN 86 bp VNTRPreeclampsia IL1RN 86 bp VNTR, TNF 850 C4TPreterm birth IL10 haplotype 1082A4819T4592A, IL1RN 86 bp VNTR, IL4 590 C4T, IL6 174 C4G, MBL2

G54D, TNF haplotype+488A4238G4308GPreterm delivery ACE int.16 ins./del., IL1B +3953 C4T, IL1RN 86 bp VNTR, MTHFR +677 C4T, TNF 863 C4APreterm newborns IL1RN 86 bp VNTRPreterm premature rupture ofmembrane

IL1RN 86 bp VNTR, HSP702 +1267, TNF 307 G4A

Primary open-angle glaucoma IL1B +3953 C4T, TNF 307 G4AProstate cancer IL1B +3953 C4TPsoriasis CDSN +1243 C4T, CDSN +619 T4C, IL10 1117 T4C, IL10 627 C4A, IL19 rs2073186, IL19 rs2243174,

IL19 rs2243188, IL19 rs2243191, IL19 rs2243193, IL1B 511 C4T, IL20 1053 T4G, IL20 gene rs2981572,IL20 rs2232360, IL20 rs2981573, LTA +252 A4G, MIF 173 G4C, MIF 714 tetra nucleotide repeat, TNF237 G4A

Psoriasis vulgaris IL12B 1188 A4CPsoriatic arthritis MICA microsat., MICB microsat., TNF 237 G4A, TNF 307 G4APulmonary tuberculosis IL10 1117 T4C, TNF 307 G4ARecurrent aphthous stomatitis IL1B 511 C4T, IL1RN 86 bp VNTR, IL6 174 C4GRecurrent hepatitis C virus IFNG +874 A4TRecurrent pregnancy loss IFNG +874 A4T, IL10 1117 T4C, IL1B 31 T4C, IL1B 511 C4T, IL6 634 C4GRecurrent spontaneous abortion IL1RN 86 bp VNTR, IL6 174 C4GReflux nephropathy TNF 307 G4ARenal allograft rejection TGFB1 869 C4T, TGFB1 915 G4C, TNF 307 G4ARenal cell carcinoma IL10 1117 T4CRenal parenchymal scarring TGFB1 509 C4T, TGFB1 800 G4A, TGFB1 869 C4TRenal transplant outcome IL2 330 T4GRenovascular disease IL10 1117 T4C, IL10 627 C4A, IL10 854 T4CRespiratory syncytial virus IL10 627 C4A, IL4 590 C4T, IL4R +148 A4G, IL4R +1902 G4TResponse to early rheumatoidarthritis treatment

LTA +252 A4G, LTA +365 G4C, LTA +720 C4A, TNF +488 G4A, TNF 237 G4A, TNF 307 G4A

Restenosis IL1B 511 C4T, IL1RN 86 bp VNTR, IL6 174 C4GRetinal artery occlusion IL6 174 C4GRheumatic heart disease TNF 237 G4A, TNF 307 G4ARheumatoid arthritis 24 microsatelites, BAT2 microsat., CTLA4 n microsat., D6S2222, D6S2223, D6S273, IL10 1117 T4C, IL10

2849 A4G, IL10.G microsat., IL1B +3953 C4T, IL1RN +2018 T4C, IL1RN 86 bp VNTR, LTA +252A4G, TGFB1 915 G4C, TNF +1304 A4G, TNF +488 G4A, TNF +851 A4G, TNF 1032 T4C, TNF237 G4A, TNF 307 G4A, TNF 863 C4A, TNFa microsat., TNFb TNFc TNFd TNFe D6S273, TNFdmicrosat., TNFRSF1A +36 A4G, TNFRSF1B +676 G4T, TNFRSF1B microsat., VEGF +936 C4T, VEGF1154 G4A, VEGF 2578 C4A, VEGF 634 C4G

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displayed on the web pages, although grouped fairlyconveniently into by gene and by disease pages, andwith separate pages for TNF superfamily and for otherentries, cannot be sorted further by the user within the

site. For this reason, separate and sortable copies of thedatabase are supplied in Microsoft Excel spreadsheetformat, available from the download page. Searcheswithin the website for individual genes, polymorphisms

Table 1 Continued

Disease Yes

Sarcoidosis CCL5 403 G4A, IFNG intron 1 CA rep., IL18 137 G4C, IL18 607 C4A, IL1A 889 C4T, TNF 857C4T

Schizophrenia CTLA4 +49 A4G, IL10 627 C4A, IL10 GCC homozygotes, IL1B 511 C4T, IL1RN 86 bp VNTR, LTA+252 A4G, TNF 307 G4A

Scleroderma TNF 863 C4ASepsis IL10 137 G4C, IL10 627 C4A, IL1RN 86 bp VNTR, LTA +252 A4GSepsis mortality TNF 307 G4ASeptic shock HSP702 +1267, LTA +252 A4G, TNF 307 G4ASepticemia IL6 174 C4GSerum lipoproteins CD14 159 C4TSevere acute pancreatitis TNF 307 G4A, TNF 1032 T4C, TNF 857 C4T, TNF 863 C4ASevere Alzheimers IL1B 511 C4TSevere aplastic anemia TNF 307 G4ASevere chronic periodontitis IL10 1117 T4CSevere dementia IL1RN 86 bp VNTRSevere gastric inflammation IL1B 511 C4TSevere hepatic fibrosis IFNG +2109 A4G, IFNG +3810 G4ASevere rheumatoid arthritis IL1B +3953 C4TSevere sepsis IL10 1117 T4C, TLR4 +896 A4G, TNF 307 G4ASevere silicosis TNF 237 G4A, TNF 307 G4A, TNF 375 G4ASevere stroke IL6 174 C4GSeverity of HCV-related liverdisease

MCP1 2518 A4G

Sjogrens syndrome CCR5 32-bp del., TNF 307 G4A, IL1B 31 T4C, IL1B 3877, IL1B 511 C4TSmoking mono-S-RCCX-TNF2 haplotype, IL6 174 C4GSpondyloarthropathy CD14 159 C4TSpontaneous abortions IL1RN 86 bp VNTRSpontaneous preterm birth IL4 590 C4T, TNF 307 G4A, IL6 174 C4GStroke IL4 590 C4T, PAI1 +11053 T4GSubacute sclerosingpanencephalitis

IL4 590 C4T

Sudden infant death syndrome IL6 1753 C4G, IL6 174 C4G, IL6 2954 G4C haploypesSynthetic hemodialysis graftfailure

TNF 307 G4A

Systemic lupus erythematosus C4AQ0, CCL5 28 C4G, IL10 1117 T4C, IL10 Haplotype 3575 T 2763C 1082A 819 T 592A,IL1A +4845 G4T, IL1A 889 C4T, IL1B +3953 C4T, IL1B 511 C4T, IL1RN 86 bp VNTR, IL8 845T4C, MBL2 G57E, MBL2 221 X4Y, MBL2 550 H4L, MBL2 G54D, MBL2 R52C, MCP1 2518 A4G,OPN +1239 A4C, OPN 156 G del., TNF 307 G4A

Systemic lupus erythematosus TNF 307 G4ASystemic sclerosis IL1A +4729 T4C, IL1A +4845 G4T, IL1A 889 C4T, MCP1 2518 A4GTransplant-related mortality IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, TNF 1032 T4C, TNF 237 G4A, TNF 307 G4A,

TNFa microsat., TNFd microsat., TNFd microsat.Tuberculosis IL12B int. 2 ATT, IL12B promoter, intron 2, intron 4, 30 UTR haplotypes, IL12RB1 haplotype 2: 641G 684 T

1094C 1132C, TNF 237 G4A, TNF 307 G4AType I diabetes mellitus IL10 1117 T4C, IL10 627 C4A, IL10 854 T4C, IL12B int. 2 ATT, IL12B +1159 C4A, IL4R +1124

A4C, IL4R +1417 G4T, IL4R +1466 T4C, IL4R +148 A4G, IL4R +1682 T4C, IL4R +1902 G4T, IL4R+676 C4T, IL4R 3223 C4T, IL4R S761P haplotypes, TNF 307 G4A, TNF microsat., IL1B +3953 C4T,IL6 174 C4G, IL18 137 G4C, IL18 607 C4A, TNFRSF1A 383 A4C

Type II diabetes mellitus APM1 haplotype 11391 11377, IL6R +48867 A4C, TNF 307 G4A, IL6 174 C4G, TNF 863 C4A,CD14 159 C4T

Ulcerative colitis IL11.A142 dinucleotide rep., IL1RN 86 bp VNTR, MIF 173 G4C, TNF 237 G4A, TNF 307 G4AUnstable angina TNF 307 G4AUrinary tract infection LTA +365 G4C, TNF 237 G4AUVB-inducedimmunomodulation

IL1B +3953 C4T

Vaginal immune defense TLR4 +896 A4GVascular morphology OPG 950 T4CViral hepatitis C TNF 307 G4AVulvar carcinogenesis IL1RN 86 bp VNTRVulvar vestibulitis syndrome IL1B +3953 C4T, IL1RN 86 bp VNTRWaist-to-hip ratio LTA +252 A4G, TNF 307 G4AWegeners granulomatosis IL10 1117 T4C, IFNG +874 A4T, TNF 237 G4A

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or diseases can however be accomplished in a webbrowser by using the Edit. Find (on This Page) menucommand.

References

1 Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T,McDermott MF et al. Cytokine gene polymorphism in humandisease: on-line databases. Genes Immun 1999; 1: 319.

2 Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T,McDermott MF et al. Cytokine gene polymorphism in human

disease: on-line databases. Genes Immun 2001; 2 (Suppl 1):6170.

3 Haukim N, Bidwell JL, Smith AJ, Keen LJ, Gallagher G,Kimberly R et al. Cytokine gene polymorphism in humandisease: on-line databases. Genes Immun 2002; 3 (Suppl 2):313330.

4 Hinrichs AS, Karolchik D, Baertsch R, Barber GP, BejeranoG, Clawson H et al. The UCSC genome browser data-base: update 2006. Nucleic Acids Res 2006; 34 (Database issue):D590D598.

5 Riva A, Kohane IS. A SNP-centric database for the inves-tigation of the human genome. BMC Bioinformatics 2004;5: 33.

Figure 1 Screenshot from the Links Navigator page on the Cytokine Gene Polymorphism in Human Disease website showing a part of thenew design.

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