The S267F variant was found more frequently among HCs (16%) compared to HBV-infected (6%) and HBV-HDV co-infected patients (3%) (HBV patients vs HC: OR=0.32, P=0.00002 and HDV patients vs. HC: OR=0.17, P=0.018).
Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3' untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated.
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.
The S267F variant may be a protective factor to resist chronic hepatitis B progression which showed a higher bile acid level in Chinese Han chronic HBV infection patients.
The S267F variant on the NTCP gene is independently associated with sustained normalization of ALT following treatment with PEG-IFN in patients with HBV infection who are HBeAg-positive.
In conclusion, the S267F variant of NTCP is clinically associated with a lower risk of chronic HBV infection and cirrhosis development, which implicates suppressing HBV entry could reduce the disease burden.
The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection.
Meta-analysis also showed that NTCP rs2296651-GA was inversely associated with HBV infection [OR(95%CI)=0.532(0.287-0.986), <i>p</i>=0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), <i>p</i>=0.001, recessive].
The p.Ser267Phe variant was associated with healthy status (P = 5.7 × 10(-23) , odds ratio = 0.36) irrespective of hepatitis B virus surface antibody status (P = 6.2 × 10(-21) and 1.5 × 10(-10) , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls).
The NTCP S267F variant of the SLC10A1 gene exhibits protective effects against HBV and HDV infection and is associated with a reduced risk of developing to advanced stages of LC and HCC.
The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations.
Meta-analysis also showed that NTCP rs2296651-GA was inversely associated with HBV infection [OR(95%CI)=0.532(0.287-0.986), <i>p</i>=0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), <i>p</i>=0.001, recessive].
Association of the S267F variant on NTCP gene and treatment response to pegylated interferon in patients with chronic hepatitis B: a multicentre study.