Abstract
Background: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal (GI) disorder. Although the mucosal histology of the GI tract is normal, low grade inflammation is considered as an underlyingmechanism in IBS. Imbalances in proand anti-inflammatory cytokines and polymorphisms of cytokines genes have been observed in some studies. However, studies on cytokine gene polymorphisms have not revealed consistent genetic features in these patients, possibily due to lack of statistical power, small sample sizes and differences in ethnicities. To overcome this problem, we performed a systematic review and meta-analysis on the case-control studies which investigated cytokine gene polymorphisms in IBS patients vs. healthy controls. Methods: A MEDLINE and EMBASE search of the literature was performed. Cytokine gene polymorphisms which had been investigated in at least 2 published studies were included. Pooled odds ratios (OR) with 95% confidence interval (95%CI) for the genotypes and allelic distributions were calculated using randomor fixed-effects models. Results: Five case-control studies were identified. IL-10 (−1082 G/ A), TGF-β1 (+869T/C and +915G/C) and TNF-α (−308G/A) were investigated in 5, 3 and 4 studies, respectively. A total of 529 IBS patients and 860 controls were included. High producer IL-10 (−1082 G/G) (OR: 0.68 [95%CI: 0.50-0.91]), intermediate producer TGFβ1 (+869T/C) (OR: 0.64 [95%CI: 0.45-0.91]) and intermediate producer TGF-β1 (+915G/ C) (OR: 0.55 [95%CI: 0.32-0.97]) genotypes were associated with a decreased risk of IBS. No associations were found between IBS and TNF-α (-308G/A) genotypes. Moreover, there was no significant association between the frequency of alleles of each polymorphism and IBS. Conclusion: Results from this meta-analysis suggest a role for IL-10 and TGF-β1 polymorphisms in IBS. Whether the changes in IL-10 and TGF-β1 producer genes translate to alterations in the levels of these cytokines in the gut wall and the nature of their protective role need further investigations.
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