Genetic variants in NTCP exon gene are associated with HBV infection status in a Chinese Han population

Wennan Wu; Yongbin Zeng; Jinpiao Lin; Yingying Wu; Tianbin Chen; Zhen Xun; Qishui Ou

doi:10.1111/hepr.13007

Genetic variants in NTCP exon gene are associated with HBV infection status in a Chinese Han population

Hepatol Res. 2018 Apr;48(5):364-372. doi: 10.1111/hepr.13007. Epub 2018 Feb 21.

Authors

Wennan Wu^{1

2}, Yongbin Zeng^{1

2}, Jinpiao Lin^{1

2}, Yingying Wu^{1

2}, Tianbin Chen^{1

2}, Zhen Xun^{1

2}, Qishui Ou^{1

2}

Affiliations

¹ First Clinical College, Fujian Medical University, Fuzhou, China.
² Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

PMID: 29205714
DOI: 10.1111/hepr.13007

Abstract

Aim: Sodium taurocholate co-transporting polypeptide (NTCP) plays an important role in the enterohepatic circulation of bile acids. Recently, NTCP was identified as a hepatitis B virus (HBV) receptor. The aim of this study is to investigate the association of NTCP polymorphisms with HBV clinical outcomes and investigate the relationship between NTCP polymorphisms and the serum bile acid level in a Chinese Han population.

Methods: The single nucleotide polymorphisms rs2296651 and rs4646285 were genotyped in 1619 Chinese Han individuals. Improved multiple ligase detection reaction was utilized to genotype. The level of bile acids was measured by the enzymatic cycling method. Quantitative polymerase chain reaction analysis was carried out to analyze the potential function.

Results: In logistic regression analysis, the frequency of rs2296651 (S267F) CT genotype was higher in HBV immune recovery and healthy control groups than in the chronic HBV infection group (P = 0.001 and P < 0.001, respectively). Patients who carried allele T showed a higher bile acid level than patients who did not carry allele T (P = 0.009). The rs4646285 AA genotype was more common in the immune recovery group than in the chronic HBV infection group (P = 0.011). No difference in serum bile acid was detected between the rs4646285 wild-type patients and mutant-type patients. Quantitative reverse transcription-polymerase chain reaction showed the NTCP mRNA levels were lower in rs4646285 variants than wild types.

Conclusion: NTCP gene polymorphisms may be associated with the natural course of HBV infection in a Chinese Han population. 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 rs4646285 variants could influence the expression of NTCP at the level of transcription, and ultimately may be associated with HBV infection immune recovery.

Keywords: bile acid; clinical outcome; hepatitis B virus; single nucleotide polymorphism; sodium taurocholate co-transporting.