Abstract
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). We tested the effects of S267F in 1117 Han Chinese patients with various HBV infection outcomes using multivariate logistic regression analysis. 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. 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.
Highlights
Sodium taurocholate cotransporting polypeptide (NTCP, SLC10A1) is a hepatocyte receptor for hepatitis B virus (HBV) infection
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 associated with reduced risk for cirrhosis (n = 192, 0.5%) and hepatocellular carcinoma (HCC) (n = 258, 1.0%) compared to those with chronic HBV infection (n = 202, 3.0%); OR 0.15 and OR 0.21, respectively
The S267F variant for the HBV cell-entry receptor Na+-taurocholate cotransporting polypeptide (NTCP) was associated with increased resistance to HBV infection and decreased risk for cirrhosis and liver cancer among those with chronic HBV infection
Summary
We tested the effects of S267F in 1117 Han Chinese patients with various HBV infection outcomes using multivariate logistic regression analysis. A protocol review committee at National Institute of Health approved the study design and questionnaire. An internal review board at the National Institute of Health approved the study (IRB number 02CN323-D). Local internal review board approvals from participating hospitals and written informed consent from participants were obtained. Following a recruitment plan designed for HBV genetic association studies, we enrolled self-reported Han Chinese participants between 2003 and 2007 in several major hospitals specializing in infectious diseases, in Beijing and other cities in Northern China [17]. All recruited participants were ≥40 years old at enrollment, allowing sufficient time for HBV exposure and disease development. We excluded patients with other hepatic viral infections or coinfection (hepatitis A virus, hepatitis C virus, hepatitis D virus, or hepatitis E virus), autoimmune conditions, alcoholic hepatitis, and drug-induced hepatitis
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