Cytokine gene polymorphisms are associated with irritable bowel syndrome: a systematic review and meta-analysis.
BACKGROUND
Low-grade inflammation has been increasingly implicated in the pathophysiology of irritable bowel syndrome (IBS). Imbalances of pro- and anti-inflammatory cytokines and polymorphisms in cytokine genes have been reported in IBS; however, these findings have not been consistently observed. This may be due to small sample sizes and differences in ethnicities. Therefore, we performed a meta-analysis on the studies that investigated cytokine gene polymorphisms in IBS patients compared to healthy controls.


METHODS
A PubMed and EMBASE search was performed, and cytokine gene polymorphisms, which had been investigated in at least two case-control studies, were evaluated. Pooled odds ratios (OR) for the genotypes were calculated using random- or fixed-effects models.


RESULTS
Five studies that investigated interleukin-10 (IL-10; -1082 G/A), transforming growth factor-β1 (TGF-β1; +869 T/C and +915 G/C) and tumor necrosis factor (TNF; -308 G/A) polymorphisms in IBS patients and controls were included. High producer IL-10 (-1082 G/G; OR: 0.64 [95% CI: 0.48-0.87]) was significantly associated with a decreased risk of IBS. The intermediate producer TGF-β1 (+915 G/C) genotype showed a tendency toward decreasing the risk of IBS. No associations were found between TNF (-308 G/A) genotypes and IBS in the whole meta-analysis although an analysis of Asian studies revealed an association between TNF (-308 G/A and G/G) genotypes and IBS (OR: 0.50 [95% CI: 0.29-0.85]), and 1.82 [95% CI: 1.08-3.07], respectively).


CONCLUSIONS
This meta-analysis indicates a role for IL-10 polymorphisms in IBS in general and TNF in Asian populations. Whether or not gene polymorphisms are associated with alterations in cytokine levels leading to functional effects at the level of the gut needs further investigation.
Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. mbashash@ucalgary.ca
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Bashashati
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Rezaei
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Bashashati
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Shafieyoun
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Daryani
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Sharkey
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Storr
D016207:Cytokines / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D043183:Irritable Bowel Syndrome / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10