Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
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Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.
This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.
Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position −174 (P = 0.002), and TNF-α G allele at position −238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (−174) and TNF-α GG genotype (−238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (−174) and TNF-α GA genotype (−238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (−174, nt565) GG haplotype and TNF-α (−308, −238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P < 0.001).
IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.
KeywordsGenetic polymorphism irritable bowel syndrome IL-6 TNF-alpha
This research has been supported by Tehran University of Medical Sciences and Health Services grant. The authors are very grateful for all colleagues in the Department of Immunology, School of Medicine, Tehran University of Medical Sciences for their kind help and advices in the laboratory and all the patients and their families for their kind collaboration in this study.
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