Senhaji Nezha, Kassogue Yaya, Fahimi Mina, Serbati Nadia, Badre Wafaa, Nadifi Sellama
Laboratory of Genetics and Molecular Pathologies, Faculty of Medicine and Pharmacy of Casablanca, Casablanca, Morocco.
Gastroenterology Department, CHU Ibn Rochd, Casablanca, Morocco.
Mediators Inflamm. 2015;2015:248060. doi: 10.1155/2015/248060. Epub 2015 Oct 28.
Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.
炎症性肠病(IBD)是由环境和遗传因素导致的多因素疾病。MDR1和GSTs基因的多态性可能解释个体对IBD易感性的差异。我们开展了一项病例对照研究,以检验MDR1(C1236T和C3435T)、GSTT1和GSTM1基因多态性与IBD风险的关联。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对MDR1基因进行基因分型,采用多重聚合酶链反应对GSTT1和GSTM1进行基因分型。进行荟萃分析以检验变异等位基因携带与IBD风险的关联。我们报告,GSTT1无效基因型与克罗恩病(CD)风险(比值比:2.5,可信区间:1.2 - 5,P = 0.013)和溃疡性结肠炎(UC)风险(比值比:3.5,可信区间:1.5 - 8.5,P = 0.004)显著相关,并且可影响克罗恩病的病情。GSTT1和GSTM1基因之间的相互作用表明,联合无效基因型与UC风险相关(比值比:3.1,可信区间:1.1 - 9,P = 0.049)。此外,与联合的1236CC/CT基因型相比,MDR1基因的1236TT基因型与UC风险相关(比值比:3.7,可信区间:1.3 - 10.7,P = 0.03)。荟萃分析表明,IBD患者中3435T携带频率显著更高。我们的结果表明,GSTT1无效和MDR1基因多态性可能在IBD易感性中起作用。