Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; 108 Military Central Hospital, Hanoi, Vietnam.
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; Vietnam Military Medical University, Hanoi, Vietnam.
Int J Infect Dis. 2019 Mar;80:147-152. doi: 10.1016/j.ijid.2019.01.038. Epub 2019 Jan 24.
To determine potential associations of the rs2296651 variant (c.800C>T, S267F) of NTCP with HBV and HBV plus concomitant HDV infection as well as with the progression of related liver diseases.
The S267F variant was genotyped by DNA sequencing in 620 HBV-infected patients and 214 healthy controls (HCs). Among the patients, 450 individuals were tested for HDV by a nested PCR assay. Logistic regression was applied to examine the association.
The S267F variant was found more frequently among HCs (16%) compared to HBV-infected (6%) and HBV-HDV co-infected patients (3%) (HBV patients vs HC: OR=0.32, P=0.00002 and HDV patients vs. HC: OR=0.17, P=0.018). The frequency of S267F variant was inversely correlated with CHB, LC or HCC patients compared with HCs (OR=0.31, P=0.001; OR=0.32, P=0.013; OR=0.34, P=0.002, respectively). S267F variant was also associated with decreased risk of the development of advanced liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (Child B and C vs. Child A, OR=0.26, adjusted P=0.016; BCLC B,C,D vs. BCLC A, OR=0.038, P=0.045, respectively). In addition, patients with the genotype CT had lower levels of AST, ALT, total and direct bilirubin as well as higher platelet counts, indicating an association with a more favorable clinical outcome.
The NTCP S267F variant of the SLC10A1 gene exhibits protective effects against HBV and HDV infection and is associated with a reduced risk of developing to advanced stages of LC and HCC.
确定 NTCP 基因 rs2296651 变体（c.800C>T，S267F）与 HBV 和 HBV 合并 HDV 感染以及相关肝病进展的潜在关联。
通过 DNA 测序对 620 例 HBV 感染患者和 214 例健康对照（HC）进行 S267F 变体基因分型。在患者中，通过巢式 PCR 检测 450 例个体的 HDV。应用逻辑回归检验相关性。
与 HBV 感染患者（6%）和 HBV-HDV 合并感染患者（3%）相比，HC 中更频繁地发现 S267F 变体（16%）（HBV 患者与 HC：OR=0.32，P=0.00002 和 HDV 患者与 HC：OR=0.17，P=0.018）。与 HCs 相比，S267F 变体的频率与 CHB、LC 或 HCC 患者呈负相关（OR=0.31，P=0.001；OR=0.32，P=0.013；OR=0.34，P=0.002）。S267F 变体还与降低进展性肝硬化（LC）和肝细胞癌（HCC）的风险相关（Child B 和 C 与 Child A，OR=0.26，调整后 P=0.016；BCLC B，C，D 与 BCLC A，OR=0.038，P=0.045）。此外，基因型 CT 的患者 AST、ALT、总胆红素和直接胆红素水平较低，血小板计数较高，提示与更有利的临床结局相关。
SLC10A1 基因的 NTCP S267F 变体对 HBV 和 HDV 感染具有保护作用，与降低发展为 LC 和 HCC 晚期阶段的风险相关。
