S0483 Cytokine Gene Polymorphisms in Irritable Bowel Syndrome vs Inflammatory Bowel Disease: A Network Meta-Analysis

Abstract

INTRODUCTION: Cytokines are imbalanced in irritable bowel syndrome (IBS) and polymorphisms of cytokine-encoding genes may alter the risk of developing IBS. Whether IBS and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are separate entities or are on a spectrum with overlap is a question which has not been sufficiently explored. This study aimed to understand whether cytokine gene polymorphisms which are observed in IBS are also associated with IBD. METHODS: We designed a network meta-analysis to compare the distribution of three cytokine gene polymorphisms that have been more frequently studied in IBS and IBD: IL-10 (-1082GA), IL6 (-174GC), and TNF-α (-308GA). PubMed and Embase were searched for studies on the distribution of these polymorphisms in IBS and IBD vs. control. NetMetaXL (CADTH, Ottawa, Canada) was used for conducting this Bayesian network meta-analysis. Vague prior <0.5 suggested lower heterogeneity where fixed effects model was used. Odds ratio (OR) with 95% credible intervals [95% Cr.I.]. was used for the comparisons. RESULTS: Ten studies on IBS vs. controls, one on IBS vs. IBD vs. controls, and thirty-nine comparing IBD vs. controls, were included. The high producer IL-10 (-1082GG) genotype was less frequent in IBS vs. the three other groups: Controls 0.66 [0.50–0.88], UC 0.66 [0.47–0.91], and CD 0.72 [0.52–0.98]; while the intermediate producer IL-10 (-1082GA) was more frequently observed in IBS vs. Controls and UC. When comparing the low producer IL-10 (-1082AA) genotype in IBS with either IBD groups or Controls, no significant difference was observed, while CD had a lower frequency of IL-10 (-1082AA) vs. Controls. The high producer TNF-α (-308AA) was similarly distributed in IBS vs. other groups and was less frequent in Controls vs. UC: 0.68 [0.46–0.99]. TNF-α (-308 GG and GA) was similar among the study groups. IL6 (-174GC) was less frequent in IBS vs. CD: 0.73 [0.55–0.98]; and in UC vs. CD: 0.69 [0.53–0.89]. The high producer IL6 (-174GG) was less frequent in CD vs. UC: 0.73 [0.56–0.95]; while no difference was observed in IBS vs. other groups. CONCLUSION: IL-10 (-1082GA) has a more prominent role than TNF-α (-308GA) and IL6 (-174GC) in the pathogenesis of IBS and may distinguish IBS from IBD. There is a shift toward high producer pro-inflammatory TNF-α (-308AA) and IL6 (-174GG) in UC, distinguishing it from the other groups.