Multidrug resistance 1 gene in inflammatory bowel disease: A meta-analysis

MDR1 基因是为煽动性的肠疾病(IBD ) 并且也许的致病的吸引人的候选人基因对治疗的反应，与在功能、基因的层次的证据。它的产品， P-glycoprotein (P-gp ) 作为因此影响许多药的布置和反应的 transmembrane 流出泵工作，一些(即 glucocorticoids ) 对 IBD 中央治疗。另外， P-gp 高度在许多上皮的表面被表示，包括的胃肠道(官方补给) 与在减少的一个通常认为的角色吸收内长或外毒素，并且也许主人细菌相互作用。MDR1 基因的许多基因变化被描述了，在为不同 P-gp 表示的一些例子证据，也，药新陈代谢被提供了。然而，数据经常由于采用的基因异质和不同方法论正在冲突。也许，在官方补给的道的 P-gp 的生理的重要性的证据的最大的片来自对老鼠建模的 mdr1 大美人的描述，它在特定的没有病原体的环境开发自发的大肠炎。学习调查到 IBD 的基因多型性和倾向也显示出冲突结果的 MDR1，由于在复杂疾病的已知的困难，特别当建议基因贡献是弱的时。在这研究，我们承担了在 IBD 与二 SNP 多型性(C3435T 和 G2677T/A ) 获得的可得到的调查结果的元分析；3435T 等位基因和 3435TT 遗传型的一个重要协会与 UC 被发现了(或 = 1.17， P = 0.003 并且或 = 1.36， P = 0.017，分别地) 。在对比，有 CD 和 G2677T/A 多型性的协会都不能被表明。

The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease （IBD） and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein （P-gp） functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom （i.e. glucocorticoids） central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract （G-I） with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdrl knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a metaanalysis of the available findings obtained with two SNPs polymorphism （C3435T and G2677T/A） in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC （OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively）. In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.