Abstract：
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.
摘要：
牛磺胆酸钠共转运多肽（NTCP），胆汁酸转运蛋白,在调节胆汁酸水平和影响HBV感染风险中起着至关重要的作用。SLC10A1基因的遗传变异，编码NTCP，影响这些功能。然而,SLC10A1基因变异对代谢和生化性状的影响尚不清楚.我们的目的是调查SLC10A1基因变异与临床和生化参数的关联，以及台湾人群中不同HBV感染状态和胆结石疾病的风险。使用Axiom全基因组CHB阵列分析了来自117,679台湾生物库参与者的基因分型数据。区域图关联分析显示SLC10A1rs2296651基因型与血脂谱之间的全基因组显著关联，γ谷氨酰转移酶（γGT）水平和抗HBc阳性。基因型-表型关联分析显示总胆固醇显著降低，低密度脂蛋白（LDL）胆固醇和尿酸水平，在罕见的rs2296651-A等位基因携带者中，较高的γGT水平和较高的胆结石发生率。具有rs2296651AA基因型的参与者表现出抗HBc阳性率和HBsAg阳性率显着降低。与GG基因型相比，非GG基因型的个体降低了各种HBV感染状态的风险：AA基因型显示出大大降低的风险，而GA基因型显示风险较低。预测工具还表明，rs2296651变体可能会诱导蛋白质损伤和致病作用。总之,我们的数据揭示了SLC10A1rs2296651基因型对生化性状水平以及HBV感染和胆结石疾病风险的多效性作用.这证实了SLC10A1的多功能性，并暗示其基因型在预测生化性状和疾病易感性方面。
