Association between NTCP gene polymorphisms with disease progression of hepatitis B infection.
Keywords:
Hepatitis B virus (HBV), chronic HBV infection (CHB), spontaneous HBV clearance, hepatocellular carcinoma (HCC), single nucleotide polymorphisms (SNPs), sodium dependent taurocholate co-transporting polypeptide (NTCP)Abstract
Background : Sodium taurocholate co-transporting polypeptide (NTCP) has been recently identified as the cellular receptor of hepatitis B virus (HBV). In addition, nucleotide polymorphisms (SNPs) in the NTCP gene are shown to be associated with developing chronic HBV infection in the Han Chinese population. However, it is unclear whether SNPs are related to the clinical outcome of HBV infection in the Thai population.
Objective : The aim of this study was to investigate the association of NTCP polymorphism with chronic HBV infection (CHB) and HCC progression.
Methods : We recruited 242 healthy controls without previous HBV exposure, 230 individuals with spontaneous HBV clearance and 635 patients with chronic hepatitis B (CHB). Among the CHB group, 319 patients were diagnosed with hepatocellular carcinoma (HCC). SNPs (rs2296651) of NTCP were detected by allelic discrimination assay using real-time polymerase chain reaction with TaqMan probe. Statistical analysis was performed using unpaired t-test, analysis of variance (ANOVA) and Chi-square test.
Results : The frequencies of GG, GA and AA genotypes of rs2296651 in healthy controls were 74.2%, 22.1% and 3.7%, respectively. The corresponding genotypes in the HBV clearance group were 84.1% 15.1% and 0.8%, while their frequencies in the CHB group were 85.0%, 13.4% and 1.6%, respectively. Compared with healthy controls, the distribution of non-GG (GA and AA) genotypes were significantly lower in the HBV clearance group [odds ratio (OR) 0.54; 95 % CI (0.35 - 0.86), P = 0.001] and the CHB groups (0.51; 0.35 - 0.73, P < 0.001). However, there was no difference in their frequencies between the HBV clearance and CHB groups. The role of SNPs in relation to HCC development was further analyzed in the CHB groups. There was no difference in the distribution of SNP between patients with or without HCC.
Conclusion : In this report, GA or AA genotypes of rs2296651 were more prevalence in non-HBV infected population. However, SNP rs2296651 did not contribute to spontaneous HBV clearance, developing CHB and HCC occurrence.
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