Role of Tumor Necrosis Factor-α and Interleukin-10 Gene Polymorphisms in Irritable Bowel Syndrome

van der Veek, Patrick P. J.; van den Berg, Marlies; de Kroon, Yvette E.; Verspaget, Hein W.; Masclee, Ad A. M.
November 2005
American Journal of Gastroenterology;Nov2005, Vol. 100 Issue 11, p2510
Academic Journal
OBJECTIVES: Imbalances in the genetically controlled pro- and anti-inflammatory cytokine production may promote ongoing low-grade inflammation after an acute gastroenteritis, and subsequently, irritable bowel syndrome (IBS) (post-infectious IBS, PI-IBS). We studied gene promoter single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α, pro-inflammatory) and interleukin-10 (IL-10, anti-inflammatory) in IBS patients and controls. METHODS: DNA was extracted from peripheral blood leucocytes of 111 IBS patients and 162 healthy controls. Genotype and allele frequencies were assessed by analyzing SNPs at position −308 (TNF-α) and −1082 and −819 (IL-10). RESULTS: Homozygous high producers for TNF-α (A/A) were rare (overall prevalence 2.6%). The heterozygous TNF-α genotype (G/A, high producer) was significantly more prevalent in IBS compared to controls (41% vs 26%, p= 0.02). More patients (41%) than controls (30%) were positive for the A allele ( p= 0.044; odds ratio (OR) 1.68, 95% confidence interval (CI) 1.01–2.79), with a similar trend for diarrhea (54%) versus constipation and alternating subtypes (<33%, p= 0.079), but not for subgroups according to a history of acute gastroenteritis. IL-10 genotypes were similarly distributed in patients and controls for both SNPs. Possession of a high producer TNF-α and a low producer IL-10 genotype were significantly more prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03–9.36) and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026). CONCLUSIONS: Our results support the emerging hypothesis that genetically determined immune activity plays a role in the pathophysiology of IBS. Future studies in larger, clinically relevant, IBS subgroups are warranted to establish definite associations with cytokine gene polymorphisms.


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