School of Life Sciences, Tsinghua University, Beijing, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Sci Rep. 2017 Apr 21;7:46490. doi: 10.1038/srep46490.
The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene's exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.
钠牛磺胆酸共转运多肽（NTCP）由 SLC10A1 编码，最近被证明是乙型肝炎病毒（HBV）的功能性受体。SLC10A1 多态性，特别是外显子 4 中的 Ser267Phe 变体（rs2296651），在持续 HBV 感染风险方面的作用经常被研究。然而，这些研究产生了相互矛盾的结果。为了研究 SLC10A1 基因座的常见遗传变异是否与持续 HBV 感染的风险相关，在两个病例对照样本集中评估了单倍型标记和推断的单核苷酸多态性（SNPs），总共包括 2550 例（持续 HBV 感染的受试者，PI）和 2124 例（自发恢复的受试者，SR）来自中国南方的血统。为了测试 SLC10A1 基因罕见或亚多态变体是否与疾病风险相关，对 244 例患者的基因外显子进行了测序。总体而言，我们在两个样本集中均未发现 SLC10A1 的 SNPs 或单倍型与疾病显著相关。此外，未观察到覆盖 SLC10A1 的罕见变体或拷贝数变异与疾病显著相关。最后，表达数量性状基因座分析表明，可能影响 SLC10A1 表达的 SNPs 也没有显著相关性。我们的结论是，SLC10A1 基因座的遗传变异不太可能是中国南方人群持续 HBV 感染的主要危险因素。
