NTCP（SLC10A1）上的 rs2296651（S267F）变异与慢性乙型肝炎患者的慢性乙型肝炎、肝硬化和肝细胞癌的进展呈负相关。

The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B.

机构信息

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

Gut. 2016 Sep;65(9):1514-21. doi: 10.1136/gutjnl-2015-310686. Epub 2015 Dec 7.

DOI:10.1136/gutjnl-2015-310686

PMID:26642861

Abstract

OBJECTIVE

The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB.

DESIGN

The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression.

RESULTS

In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p<0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10(5) copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p<0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p<0.001).

CONCLUSIONS

The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC.

摘要

目的

牛磺胆酸钠共转运蛋白（NTCP）由 SLC10A1 编码，最近被鉴定为乙型肝炎病毒（HBV）的受体。我们评估了 SLC10A1 上 p.Ser267Phe 变异（rs2296651）与慢性乙型肝炎（CHB）患者的乙型肝炎表面抗原（HBsAg）血清阳性状态、肝硬化和肝细胞癌（HCC）之间的关联。

设计

在 3801 例 CHB 患者和 3801 例 HBsAg 血清阴性匹配个体中对变异进行了基因分型。使用逻辑回归估计变异与 CHB、肝硬化和 HCC 关联的比值比（OR）及其 95%置信区间（CI）。

结果

在 CHB 患者中，S267F 变异在 515 例（18.5%）对照、40 例（17.2%）仅肝硬化病例、49 例（13.2%）非肝硬化 HCC 病例和 52 例（12.7%）肝硬化-HCC 病例中观察到。在调整已知危险因素后，S267F 与肝硬化（OR 0.65（95%CI 0.49 至 0.86），p=0.002）和 HCC（OR 0.55（95%CI 0.42 至 0.72），p<0.001）的风险降低显著相关。这种关联在非肝硬化和肝硬化-HCC 中持续存在。与 HBV DNA 水平大于 10（5）拷贝/mL 的患者相比，HBV DNA 水平不可检测且携带 GA 或 AA 基因型的患者发生 HCC 的风险降低了 25 倍（OR 0.04（95%CI 0.02 至 0.11），p<0.001）。AA 基因型也与 HBsAg 血清阴性（OR 0.13（95%CI 0.05 至 0.34），p<0.001）相关。