A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
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DOI：
10.1038/ng2101
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发表时间：
2007-08-01
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;Schafmayer, Clemens;Hampe, Jochen
胆结石疾病（胆石症）的总体患病率为10% - 20%，是工业化国家最常见且在经济上相关的健康问题之一[1,2]。我们对280名胆结石患者和360名对照者的450万个单核苷酸多态性（SNP）进行了关联扫描。在1105名患病个体和873名对照者中对235个最显著的SNP进行的后续研究重复了ABCG8基因中SNP A - 1791411与疾病的关联（等位基因P值P - CCA = 4.1×10⁻⁹），随后发现这归因于编码变异rs11887534（D19H）。在728名德国人（P = 2.8×10⁻⁷）和167名智利受试者（P = 0.02）中也得到了进一步验证。在整个德国样本中，D19H携带者的总体优势比为2.2（95%置信区间：1.8 - 2.6，P = 1.4×10⁻¹⁴）。在胆固醇胆结石患者中关联更强（优势比 = 3.3），这表明His19可能与胆固醇更有效地转运到胆汁中有关。
With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries1,2. We performed an association scan of 4500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value P-CCA = 4.1 x 10(-9)), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 x 10(-7)) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8-2.6, P = 1.4 x 10(-14)) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile.