The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection

Cell Physiol Biochem. 2018;45(6):2540-2547. doi: 10.1159/000488272. Epub 2018 Mar 16.

Abstract

Background/aims: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection.

Methods: A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly.

Results: The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it.

Conclusion: Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.

Keywords: B and T lymphocyte attenuator; Chronic HBV infection; Single nucleotide polymorphisms.

MeSH terms

  • Adult
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / pathology
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Immunologic / genetics*

Substances

  • BTLA protein, human
  • Receptors, Immunologic