The relationship between NTCP gene varieties and the progress of liver disease after HBV infection: an updated systematic review and meta-analysis

Background: The aim of this study was to analyze the relationship between sodium taurocholate cotransporting polypeptide (NTCP) gene varieties and hepatitis B virus (HBV) infection and the progress of HBV-related liver disease.

Methods: PubMed, EMBASE, Web of Science and Cochrane library were used to search eligible studies. STATA software was performed to combine results. Pooled odds ratios (OR) was used to assess the potential genetic relationships.

Results: A total of 18 eligible case-control studies with 24960 cases and 28342 controls were included in this meta-analysis. The A allele of rs2296651 polymorphism was found to be significantly linked to a protection of HBV infection in the whole combined analysis (P = 0.000). Meanwhile, this allele was significantly associated with a decreased risk of hepatocellular carcinoma (HCC) (A vs. G: OR = 0.668, 95% CI: 0.571-0.782, P = 0.000), and was significantly associated with HBV nature clearance (A vs. G: OR = 0.744, 95% CI: 0.585-0.946, P = 0.016; AA+GA vs. GG: OR = 0.775, 95% CI: 0.613-0.980, P = 0.033; GA vs. GG: OR = 0.748, 95% CI: 0.588-0.952, P = 0.018). However, rs4646287 genetic varieties had no statistical differences in all models with HBV infection or HBV-related disease progress, liver cirrhosis, acute-on-chronic liver failure and HCC, as well as rs7154439, rs4646285, rs4646296.

Conclusions: Rs2296651 polymorphism (A allele) may protect from HBV infection and the progress of HBV-related disease (HBV-related HCC). Future research about other single nucleotide polymorphisms (SNPs) (rs4646287, rs7154439, rs4646285, rs4646296) of NTCP may be needed to clarify the relationship of NTCP gene varieties with HBV infection and HBV-related disease.