Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
Department of Research, Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No.289, Jianguo Road., Xindian Dist, New Taipei City, 23142, Taiwan.
Mol Genet Genomics. 2024 Jun 13;299(1):62. doi: 10.1007/s00438-024-02153-2.
Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.
牛磺胆酸钠共转运蛋白（NTCP）是一种胆酸转运蛋白，在调节胆酸水平和影响乙型肝炎病毒（HBV）感染风险方面发挥着关键作用。编码 NTCP 的 SLC10A1 基因的遗传变异会影响这些功能。然而，SLC10A1 基因变异对代谢和生化特征的影响仍不清楚。我们旨在研究 SLC10A1 基因变异与临床和生化参数的关系，以及在台湾人群中不同 HBV 感染状态和胆石病的风险。使用 Axiom 全基因组 CHB 数组对来自 117679 名台湾生物银行参与者的基因分型数据进行了分析。区域图谱关联分析表明，SLC10A1 rs2296651 基因型与血脂谱、γ-谷氨酰转移酶（γGT）水平和抗-HBc 阳性之间存在全基因组显著关联。基因型-表型关联分析显示，罕见 rs2296651-A 等位基因携带者的总胆固醇、低密度脂蛋白（LDL）胆固醇和尿酸水平较低，γGT 水平较高，胆石发生率较高。rs2296651 AA 基因型携带者的抗-HBc 阳性和 HBsAg 阳性率显著较低。与 GG 基因型相比，非 GG 基因型的个体发生各种 HBV 感染状态的风险降低：AA 基因型的风险显著降低，而 GA 基因型的风险适度降低。预测工具还表明，rs2296651 变异可能导致蛋白质损伤和致病作用。总之，我们的数据揭示了 SLC10A1 rs2296651 基因型对生化特征水平和 HBV 感染和胆石病风险的多效性影响。这证实了 SLC10A1 的多功能性，并暗示其基因型可预测生化特征和疾病易感性。
