Institute of Medicine, Chung Shan Medical University, Taichung City, 40201, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
BMC Gastroenterol. 2021 Dec 14;21(1):468. doi: 10.1186/s12876-021-02060-5.
Gallstones are abnormal masses caused by impaired metabolism of cholesterol, bilirubin, or bile salts in the gallbladder or biliary tract. ATP-binding cassette subfamily G member 8 (ABCG8) is a protein that regulates cholesterol efflux from the liver. Genome-wide association studies (GWAS) and meta-analyses of GWAS revealed the ABCG8 rs11887534 variant as the most common genetic determinant of gallstones in humans. These findings have not been extensively replicated in Taiwanese. Therefore, we appraised the relationship between gallstones and rs11887534 in a relatively large Taiwanese sample.
We retrieved data collected through questionnaires, physical and biochemical tests from the Taiwan Biobank Bank (TWB). The study participants comprised 7388 men and 13,880 women who voluntarily enrolled in the Taiwan Biobank project between 2008 and 2019. Gallstones were self-reported.
The overall sample size was 21,268 comprising 938 gallstone patients and 20,330 non-gallstone individuals. Among the participants, 20,640 had the GG and 628 had the GC + CC genotype. At p-value < 0.05, the baseline genotypes and gallstone status between men and women were not significantly different. The risk of gallstones was higher in participants having the GC + CC compared to the GG genotype: odds ratio (OR); 95% confidence interval (CI) = 1.698; 1.240-2.325), but was lower in men compared to women (OR = 0.763; 95% CI = 0.638-0.913). Compared to men with the rs11887534 GG genotype, women with the GG and GC + CC genotypes had a higher risk of gallstone (OR; 95% CI = 1.304; 1.087-1.565 for GG and 2.291; 1.514-3.467 for GC + CC). The positive association between GC + CC and gallstones was retained after we restricted the analysis to the female participants (OR; 95% CI = 1.789 = 1.208-2.648). Hormone use was associated with an elevated risk of gallstones (OR; 95% CI = 1.359; 1.107-1.668). Relative to GG and no hormone use, we found a significantly high risk among hormone users with the GC + CC genotype (OR; 95% CI = 3.596; 1.495-8.650).
The rs11887534 GC + CC genotype was independently associated with a higher risk of gallstones. This risk was much higher among women, especially those who used hormones for various gynecological purposes.
胆结石是由胆囊或胆道中胆固醇、胆红素或胆汁盐代谢紊乱引起的异常物质。三磷酸腺苷结合盒亚家族 G 成员 8（ABCG8）是一种调节肝脏胆固醇外排的蛋白质。全基因组关联研究（GWAS）和 GWAS 的荟萃分析显示，ABCG8 rs11887534 变体是人类胆结石最常见的遗传决定因素。这些发现尚未在台湾人群中得到广泛复制。因此，我们在一个相对较大的台湾样本中评估了胆结石与 rs11887534 之间的关系。
我们从 2008 年至 2019 年期间自愿参加台湾生物银行（TWB）项目的 7388 名男性和 13880 名女性中检索了通过问卷、身体和生化测试收集的数据。胆结石是自我报告的。
总体样本量为 21268 人，包括 938 名胆结石患者和 20330 名非胆结石个体。在参与者中，20640 人具有 GG 基因型，628 人具有 GC+CC 基因型。在 p 值<0.05 时，男性和女性之间的基线基因型和胆结石状态没有显著差异。与 GG 基因型相比，GC+CC 基因型的胆结石风险更高：比值比（OR）；95%置信区间（CI）=1.698；1.240-2.325），但男性的风险低于女性（OR=0.763；95%CI=0.638-0.913）。与 rs11887534 GG 基因型的男性相比，具有 GG 和 GC+CC 基因型的女性胆结石风险更高（OR；95%CI=1.304；1.087-1.565 对于 GG 和 2.291；1.514-3.467 对于 GC+CC）。GC+CC 与胆结石之间的正相关关系在我们将分析仅限于女性参与者时仍然存在（OR；95%CI=1.789=1.208-2.648）。激素使用与胆结石风险增加相关（OR；95%CI=1.359；1.107-1.668）。与 GG 和无激素使用相比，我们发现激素使用者中 GC+CC 基因型的风险显著升高（OR；95%CI=3.596；1.495-8.650）。
rs11887534 GC+CC 基因型与胆结石风险增加独立相关。这种风险在女性中更高，尤其是那些因各种妇科目的使用激素的女性。
