J Infect Dis. 2018 Jun 14. doi: 10.1093/infdis/jiy355. [Epub ahead of print]
The loss-of-function S267F variant in HBV receptor NTCP reduces human risk to HBV infection and disease progression.
An P1, Zeng Z2, Winkler CA1.
Author information
1
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD.
2
Department of Infectious Diseases, Peking University First Hospital, Beijing, P.R. China.
Abstract
Background:
Sodium taurocholate cotransporting polypeptide (NTCP, SLC10A1) was recently identified as a hepatocyte receptor for infection of Hepatitis B virus (HBV). The natural S267F variant in NTCP causes a loss of HBV receptor function of NTCP.
Objective:
We assessed the association of S267F with HBV resistance, HBV infection clearance, and HBV-related cirrhosis and 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-resistance healthy controls (n = 179, 4.0%) compared to HBV-infected patients (n= 648, 1.5%), with odds ratio [OR] 0.32 [95% confidence interval [CI] 0.15-0.68], p = 0.003 (dominant model). The 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%), with OR 0.15 [0.03-0.70] and OR 0.21 [ 0.062-0.72], respectively. There was no association of the S267F variant with spontaneous HBV clearance.
Conclusion:
Carriage of the S267F variant for the HBV cell-entry receptor NTCP was associated with increased resistance to HBV infection and decreased risk of development of cirrhosis and liver cancer among those with chronic HBV infection.