The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

Polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population. TaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls. Of the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR=0.588, 95% CI=0.413–0.836, P=0.003; OR=0.768, 95% CI=0.645–0.915, P=0.003, respectively. HCC vs self-limited subjects: OR=0.598, 95% CI=0.404–0.886, P=0.010; OR=0.772, 95% CI=0.635–0.940, P=0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR=0.470, 95% CI=0.288–0.766, P=0.002; OR=0.681, 95% CI=0.535–0.866, P=0.002, respectively. Liver cirrhosis vs self-limited subjects: OR=0.624, 95% CI=0.392–0.992, P=0.046; OR=0.791, 95% CI=0.627–0.998, P=0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P>0.05). The TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker. •MTHFR 677TT may confer a protective effect in HBV-HCC patients in a population with high prevalence of this allele.•Using self-limited subjects as reference, we further confirm the protective effect of MTHFR 677TT on liver disease.•The MTHFR 677TT genotype and T allele are relatively prevalent in the Tianjin population.