A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis
A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis
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DOI：
10.1038/ng.3417
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发表时间：
2015-12-01
期刊：
影响因子：
30.8
通讯作者：
Hampe, Jochen
中科院分区：
文献类型：
--
作者：
Buch, Stephan;Stickel, Felix;Hampe, Jochen
酒精滥用是肝硬化的主要原因，也是西方世界肝移植的第二大常见适应症（1-3）。我们在欧洲血统的个体（712例和1，426例对照）中进行了酒精相关肝硬化的全基因组关联研究，随后在两个独立的欧洲队列（1，148例和922例对照）中进行了验证。我们确定MBOAT 7（P = 1.03 x 10（-9））和TM 6SF 2（P = 7.89 x 10（-10））基因的变异为新的风险位点，并证实PNPLA 3中的rs738409在全基因组显著性水平上为酒精相关性肝硬化的重要风险位点（P = 1.54 x 10（-48））。这三个位点在脂质加工中发挥作用，表明脂质周转在酒精相关性肝硬化的发病机制中很重要。
Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world(1-3). We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 x 10(-9)) and TM6SF2 (P = 7.89 x 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 x 10(-48)) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.