Tumor Necrosis Factor-A Haplotype
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Transcript of Tumor Necrosis Factor-A Haplotype
8/6/2019 Tumor Necrosis Factor-A Haplotype
http://slidepdf.com/reader/full/tumor-necrosis-factor-a-haplotype 1/11
TUMOR NECROSIS FACTOR-LPHA
HAPLOTYPEIS STRONGLY ASSOCIATED
WITH BONE MINERAL DENSITY
IN PATIENTS WITH CROHN¶S DISEASE
Naomi Lee,* Elizabeth Fowler,� Susan Mason, Douglas Lincoln,§ Dennis RTaaffe* and
Graham Radford-Smith
DIPRESENTASIKAN OLEH
dr. ANANTA
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BACKGROUND
CROHN·S DESEASE
INFLAMATORY
PROSSES
GENETIC
SUSCEPTIBILITY
MALABSORPTION CORTICOSTEROID
TREATMENT
DECREASE
BONE MINERAL DENSITY
INCREASE
MOBIDITY OF DESEASE
8/6/2019 Tumor Necrosis Factor-A Haplotype
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BACKGROUND
CROHN·S
DESEASE
DIFFICULT TOQUANTIFY AND
COMPARE FROM
STUDY TO STUDY
MOLECULAR BASIS
OF COMPLEX
DISORDERS
NOD2/CARD15
CL1A1 gene
TNF haplotype genes
DECREASE
BONE MINERAL
DENSITY
CLINICAL
VARIABLES
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METHODS
304 patientsCROHN·S DESEASE
GENOTYPINGTNF CC and TNF GT
haplotype
Include: radiologic, hitologic,
endoscopic assesement
Exclude : medical condition that may
alter bone metabolism (renal or hepatic
desease, thyrotocsicosis,hyperparathiroidism,etc
STATISTICS ANALIZED
Pearson·s correlation coefficients
linear regression models (and t-tests)
analysis of variance (anova)
BONE
DENSITOMETRY
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RESULTS
Individuals with normal BMD both at the hip and spinewere significantly more likely to inherit the high-TNF CC
genotype (P = 0.002) and had a strong negative association
with the low-TNF GT haplotype (P = 0.002)
The figures for spinal BMD alone were very similar, with
significant associations betweennormal spine BMD and the
CC genotype (P = 0.003), and the strong negative
association with a GT haplotype (P = 0.005)
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RESULTS
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DISCUSION
´ Crohn·s desease is a cronic inflamatory desease.
´ A number of other studies, including measurement of circulating TNF-a in cronic inflamatory , have suggested animportant role for TNF- as a skeletal catabolic agent.
´ The Problem of difficulties in studying circulating andtissue cytokines (TNF-) becouse of their very short half-life.
´ genetically determined variation in the concentration of
TNF-a may be a more reliable method to determinewhether this cytokine plays a role in bone metabolism inthe long term
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DISCUSION
´ Present study determining a genetic association
between the TNF-a gene and bone loss by
incorporating both genotype and haplotype analysis.
´ There is strong correlation between these analyses
both for overall BMD
´ True association in the present study is between BMD
and gene that is in linkage disequilibrium with the
reported TNF-a genotypes and haplotype at 6p21
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DISCUSION
´ Other stdudy demonstrated a significantly reduced
fracture risk in patients who had undergone bowel
surgery.
´ Removal of the inflamed segment may allowtemporary relief from pro-inflammatory cytokines such
as TNF that play a key role in bone resorption
´ Crohn·s Desese patient with high TNF-a genotypes
and haplotype at 6p21 has more circulatory cytokines
such as TNF . .
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DISCUSION
´ The temporary reduction in intestinal inflammation
and associated reduction in steroid usage seen with
intestinal resection may temporarily prevent the
abnormal bone metabolism observed in patientswithout previous resection and in those with greater
duration since resection
´ More radical treatment to remove inflamatory segmen
in patient that has high TNF-a genotypes and
haplotype at 6p21 could reduce complication
decrease bone mineral density.
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