固醇转运体三磷酸腺苷结合盒转运蛋白 G8、胆石症和普通人群中 62000 人的胆道癌。
Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population.
机构信息
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
出版信息
Hepatology. 2011 Feb;53(2):640-8. doi: 10.1002/hep.24046. Epub 2010 Dec 28.
UNLABELLED
Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62,279 white individuals from The Copenhagen City Heart Study and The Copenhagen General Population Study, randomly selected to reflect the adult Danish population aged 20 to 80+ years. Endpoints were recorded from January 1976 through May 2009. During a mean follow-up of, respectively, 31 and 4.4 years, 3124 participants developed symptomatic gallstone disease and 30 developed biliary cancer. The multifactorially adjusted hazard ratio for symptomatic gallstone disease was 1.9 (95% confidence interval, 1.7-2.1) in DH heterozygotes (prevalence, 12%), and 3.3 (2.3-4.6) in HH homozygotes (0.4%) versus noncarriers (P for trend <0.001). Mean age at onset of symptomatic gallstone disease was 56 years for noncarriers, 54 for DH heterozygotes, and 52 for HH homozygotes (P for trend <0.001). The fraction of all gallstones attributed to D19H was 11%. The multifactorially adjusted hazard ratio for biliary cancer was 4.0 (1.9-8.4) in DH heterozygotes and HH homozygotes combined versus noncarriers (P < 0.001). The fraction of all biliary cancers attributed to the D19H genotype was 27%. Finally, D19H genotype associated with stepwise increases in plasma levels of alanine aminotransferase and gamma glutamyltransferase of up to 14% and 25% in HH homozygotes, and with corresponding stepwise reductions in plasma levels of total and low-density lipoprotein cholesterol of up to 5% versus noncarriers (all comparisons, P for trend <0.001).
CONCLUSION
In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.
未加标签
胆石病是胆管癌的一个危险因素，具有很强的遗传成分，但潜在的基因在很大程度上尚不清楚。为了检验载脂蛋白 G8（三磷酸腺苷结合盒转运蛋白 G8）Asp19His（D19H）基因型是否可预测普通人群中胆石症和胆管癌的风险这一假说，我们对来自哥本哈根城市心脏研究和哥本哈根普通人群研究的 62279 名白人个体进行了研究，这些个体是随机选择的，代表了 20 至 80 岁以上的丹麦成年人群。研究的终点事件从 1976 年 1 月至 2009 年 5 月记录。在平均分别为 31 年和 4.4 年的随访期间，3124 名参与者出现了有症状的胆石症，30 名参与者发生了胆管癌。在多因素校正的风险比中，DH 杂合子（患病率为 12%）的有症状胆石症为 1.9（95%置信区间，1.7-2.1），HH 纯合子（0.4%）为 3.3（2.3-4.6），而非携带者为 1.0（趋势检验 P<0.001）。非携带者、DH 杂合子和 HH 纯合子发生有症状胆石症的平均年龄分别为 56 岁、54 岁和 52 岁（趋势检验 P<0.001）。归因于 D19H 的所有胆石症的比例为 11%。DH 杂合子和 HH 纯合子的胆管癌的多因素校正风险比为 4.0（95%置信区间，1.9-8.4），而非携带者为 1.0（趋势检验 P<0.001）。归因于 D19H 基因型的所有胆管癌的比例为 27%。最后，与非携带者相比，D19H 基因型与丙氨酸氨基转移酶和γ-谷氨酰转肽酶的血浆水平分别升高 14%和 25%，以及总胆固醇和低密度脂蛋白胆固醇的血浆水平分别降低 5%相关，这些变化在 HH 纯合子中呈梯度变化（所有比较，趋势检验 P<0.001）。
结论
在该普通人群队列中，ABCG8 D19H 基因型是有症状的胆石症和胆管癌的重要预测因素。
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