The S267F variant of sodium taurocholate co-transporting polypeptide is strongly associated with resistance to chronic hepatitis B and high level of serum total bile acids

Background and aims

The sodium taurocholate co-transporting polypeptide (NTCP) is a functional receptor for the hepatitis B virus (HBV), and it is critical for bile acid homeostasis. Previous studies of the association between the S267F variant and chronic hepatitis B (CHB) have generated conflicting results. This study analyzed the correlation between the NTCP S267F variant and CHB susceptibility by using a large sample of participants classified by gender and age, and this study also analyzed the relationship between this variant and the level of serum total bile acids.

Methods

In total, 543 patients with CHB and 429 control subjects underwent S267F variant genotyping using SNaPshot technology. Logistic regression was utilized to evaluate any association of the NTCP S267F variant with CHB susceptibility.

Results

The S267F variant was inversely correlated with the risk of chronic HBV infection in both the dominant model (GG genotype vs. AG genotype: odds ratio (OR) = 0.46, 95% confidence interval (CI) 0.30–0.71, P < 0.001) and the allele model (G allele vs. A allele: OR = 0.50, 95% CI 0.33–0.76, P = 0.001), and this correlation was not affected by gender and age stratification. The carriers of the heterozygous NTCP variant exhibited higher total bile acids levels than the carriers of wild-type NTCP, regardless of whether they were control subjects or patients with CHB. Heterozygous carriers exhibited reduced hepatitis B e antigen (HBeAg)-positivity rates and had lower ALT, AST, and lg DNA concentrations compared with wild-type carriers in patients with CHB.

Conclusions

The S267F variant of NTCP is a protective factor that reduces the risk of chronic HBV infection and exhibits a higher total bile acids level. Patients with CHB who carry this variant may have a better prognosis than those carrying wild-type NTCP.