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The Role of Cytokine Gene Polymorphisms in Determining Disease Susceptibility and Phenotype in Inflammatory Bowel Disease
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The Role of Cytokine Gene Polymorphisms in Determining Disease Susceptibility and Phenotype in Inflammatory Bowel Disease
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Journal Article
The Role of Cytokine Gene Polymorphisms in Determining Disease Susceptibility and Phenotype in Inflammatory Bowel Disease
2005
Overview
Emerging data indicate that alterations in cytokine synthesis may play a role in inflammatory bowel disease (IBD) pathogenesis. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. The aim of this study was to assess the relationship between polymorphisms involving five cytokine genes (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma), and IBD susceptibility and disease phenotype.
Cytokine genotyping was performed utilizing polymerase chain reaction. The specific gene polymorphisms that were probed for included: -1082(G/A), -819(T/C), and -592(A/C) in the IL-10 promoter, -308(G/A) in the TNF-alpha promoter, codon 10 (T/C), and codon 25 (G/C) of the TGF-beta signal sequence, +874(T/A) of intron 1 of IFN-gamma, and -174(C/G) in the IL-6 promoter.
A total of 193 IBD patients (138 Crohn's disease (CD) and 55 ulcerative colitis (UC)) and 92 controls were evaluated. No association between IBD, UC, or CD susceptibility and the cytokine gene polymorphisms were found. Patients with ileocolonic CD were more likely to possess the IL-6 -174 GG genotype compared to those with nonileocolonic disease (p= 0.006). Patients with ileal CD were more likely to possess the IL-6 -174 GC genotype compared to those with nonileal disease (p= 0.0004). An increased number of CD patients with isolated colonic disease possessed the IL-6 -174 CC genotype compared to those with nonisolated colonic disease (p= 0.032).
The cytokine gene polymorphisms studied here do not appear to influence IBD susceptibility. There does, however, appear to be an influence on disease phenotype, particularly on CD site.
Publisher
Blackwell Publishing,Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
Subject
/ Biological and medical sciences
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - immunology
/ Female
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Genetic Predisposition to Disease - genetics
/ Humans
/ Inflammatory Bowel Diseases - genetics
/ Inflammatory Bowel Diseases - immunology
/ Lymphotoxin-alpha - genetics
/ Male
/ Polymorphism, Genetic - genetics
/ Polymorphism, Single Nucleotide - genetics
/ Promoter Regions, Genetic - genetics
/ Protein Sorting Signals - genetics
