A genetic variant of the NTCP gene is associated with HBV infection status in a Chinese population

BACKGROUND: To investigate whether genetic variants of the HBV receptor gene NTCP are associated with HBV infection in the Han Chinese population. METHODS: We sequenced the entire 23 kb NTCP gene from 111 HBeAg-positive HBsAg carriers (PSE group), 110 HBeAg-negative HBsAg carriers (PS group), and 110 control subjects. Then, we performed association analyses of suggestively significant SNPs with HBV infection in 1075 controls, 1936 PSs and 639 PSEs. RESULTS: In total, 109 rare variants (74 novel) and 38 single nucleotide polymorphisms (SNPs, one novel) were screened. Of the seven non-synonymous rare variants, six were singletons and one was a double hit. All three damaging rare singletons presented exclusively in the PSE group. Of the five SNPs validated in all 3650 subjects, the T allele of rs4646287 was significantly decreased (p = 0.002) in the PS group (10.1 %) and PSE group (8.1 %) compared to the controls (10.9 %) and was decreased to 7.4 % in the PSE hepatocellular carcinoma (HCC) subgroup. Additionally, rs4646287-T was associated with a 0.68-fold (95 % CI = 0.51–0.89, p = 0.006) decreased risk of PSE compared with the controls. The NTCP mRNA level was lower in HCC tissues in “CT + TT” carriers than in “CC” carriers. CONCLUSIONS: We found a genetic variant (rs4646287) located in intron 1 of NTCP that may be associated with increased risk of HBV infection in Han Chinese. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2257-6) contains supplementary material, which is available to authorized users.