Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
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DOI：
10.1007/s10875-009-9342-4
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发表时间：
2010-01-01
影响因子：
9.1
通讯作者：
Amirzargar, Ali Akbar
中科院分区：
文献类型：
--
作者：
Barkhordari, Elham;Rezaei, Nima;Amirzargar, Ali Akbar
肠易激综合症（IBS）是一种多因素功能性胃肠道疾病，其特征是反复腹痛和排便习惯改变。促炎细胞因子在肠道炎症中发挥重要作用，但其产生受到基因控制。本研究在一组IBS患者中进行，分析了编码促炎细胞因子的多个多态性基因（白细胞介素-6（IL）、肿瘤坏死因子-α（TNF-α）和IL-1组）的基因型频率。采用聚合酶链反应和序列特异性引物的方法，扩增细胞因子基因，凝胶电泳检测71例IBS患者的等位基因和基因型，并与健康对照者进行比较。分析数据结果显示，IL-1R C等位基因在Pst-I 1970位点的频率（P = 0.017），IL-6 G等位基因在位置-174（P = 0.002），患者组中-238位的TNF-α G等位基因（P < 0.001）显着高于对照组。患者组中IL-6 GG基因型（-174）和TNF-α GG基因型（-238）也显着过高（P < 0.001），而IBS患者中IL-6 CG基因型（-174）和TNF-α GA基因型（-238）显着降低（P < 0.001）。 IL-6 (-174, nt565) GG 单倍型和 TNF-α (-308, -238) GG 单倍型的频率在患者组中也显着升高 (P < 0.001)，而单倍型 IL-6 CG 和 TNF-α GA 在 IBS 患者中的频率显着降低 (P < 0.001)。 IL-6 和 TNF-α 促炎性细胞因子基因多态性可能会改变个体对IBS的易感性，并可能在疾病的病理生理学中发挥作用。
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-alpha), 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-alpha 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-alpha GG genotype (-238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (-174) and TNF-alpha 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-alpha (-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-alpha 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.