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 HBV-infected 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.