Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
Inflamm Bowel Dis. 2012 Mar;18(3):562-72. doi: 10.1002/ibd.21728. Epub 2011 Sep 1.
Inflammatory bowel disease (IBD) is a complex disease with a genetic background. Crohn's disease (CD) and ulcerative colitis (UC) are the two main types of IBD. There is indication that variants in the MDR1 gene are associated with development of IBD. However, the 20 published genetic association studies (GAS) for the three most popular variants in the MDR1 gene (C3435T, G2677T/A, and C1236T) have produced inclusive results.
In order to decrease the uncertainty of pooled risk effects and to explore the trend and stability of the risk effects, a meticulous meta-analysis, including cumulative and recursive cumulative meta-analysis, of the GAS related to the MDR1 gene with susceptibility to IBD was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G) ).
The analysis showed marginal significant association for the C3435T variant in UC: the risk estimate for the allele contrast was OR = 1.11 (1.00-1.22) and OR(G) = 1.12 (1.01-1.27), indicating that a subject with high mutational load has a 12% higher probability of being diseased. The respective cumulative meta-analysis indicated a downward trend of association, as evidence accumulates with the association being significant during the whole published period. The cumulative meta-analysis for the other variants showed lack of any trend of association. However, the recursive cumulative meta-analysis showed that there is no sufficient evidence for denying or claiming an association for all variants.
More evidence is needed to draw safe conclusions regarding the association of MDR1 variants and development of IBD.
炎症性肠病（IBD）是一种具有遗传背景的复杂疾病。克罗恩病（CD）和溃疡性结肠炎（UC）是 IBD 的两种主要类型。有迹象表明，MDR1 基因中的变异与 IBD 的发展有关。然而，针对 MDR1 基因中三个最流行变异（C3435T、G2677T/A 和 C1236T）的 20 项已发表的遗传关联研究（GAS）得出了相互矛盾的结果。
为了降低汇总风险效应的不确定性，并探索风险效应的趋势和稳定性，对与 MDR1 基因易感性相关的 GAS 进行了细致的荟萃分析，包括累积和递归累积荟萃分析。风险效应基于等位基因对比的优势比（OR）和广义优势比（OR(G)）进行估计。
分析显示 UC 中 C3435T 变异存在边缘显著相关性：等位基因对比的风险估计值为 OR = 1.11（1.00-1.22）和 OR(G) = 1.12（1.01-1.27），这表明突变负荷较高的个体患病的概率增加了 12%。相应的累积荟萃分析表明，随着证据的积累，关联呈下降趋势，整个发表期间的关联均具有统计学意义。其他变异的累积荟萃分析表明，没有任何关联趋势。然而，递归累积荟萃分析表明，没有足够的证据可以否认或声称所有变异都存在关联。
需要更多的证据来得出关于 MDR1 变异与 IBD 发展之间关联的安全结论。
