The loss-of-function S267F variant in HBV receptor NTCP reduces human risk for HBV infection and disease progression

Abstract

Background. Sodium taurocholate cotransporting polypeptide (NTCP, SLC10A1) is a hepatocyte receptor for hepatitis B virus (HBV) infection. The natural NTCP S267F variant causes loss of NTCP HBV receptor function. We assessed the association of S267F with HBV resistance, HBV infection clearance, and HBV-related cirrhosis and hepatocellular carcinoma (HCC). Methods. We tested the effects of S267F in 1117 Han Chinese patients with various HBV infection outcomes using multivariate logistic regression analysis. Results. The frequency of S267F (T allele) was higher in HBV-resistant healthy controls (n = 179, 4.0%) compared to HBVinfected patients (n = 648, 1.5%); odds ratio (OR) 0.32 (95% confidence interval [CI] 0.15-0.68; P = .003; dominant model). 267F variant genotypes were also associated with reduced risk for cirrhosis (n = 192, 0.5%) and HCC (n = 258, 1.0%) compared to those with chronic HBV infection (n = 202, 3.0%); OR 0.15 (95% CI, 0.03-0.70) and OR 0.21 (95% CI, 0.062-0.72), respectively. There was no association of the S267F variant with spontaneous HBV clearance. Conclusion. The S267F variant for the HBV cell-entry receptor NTCP was associated with increased resistance to HBV infection and decreased risk for cirrhosis and liver cancer among those with chronic HBV infection.