Association between cytotoxic T-lymphocyte associated protein 4 gene +49 A/G polymorphism and chronic infection with hepatitis B virus: a meta-analysis

J Int Med Res. 2013 Jun;41(3):559-67. doi: 10.1177/0300060513483387. Epub 2013 May 13.

Abstract

Objective: This meta-analysis determined the relationship between polymorphisms of the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene and hepatitis B virus (HBV) clearance in chronic hepatitis B.

Methods: Published studies reporting associations between CTLA4 gene +49A/G polymorphisms and chronic HBV infection were reviewed. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the risk of persistent HBV according to genotype.

Results: Six studies, involving 1076 chronic HBV patients and 1294 controls, were included. The risk of persistent HBV in patients with a +49 GG/AG genotype decreased significantly compared with the AA genotype (OR 0.65; 95% CI 0.52, 0.82). The variant G allele was negatively associated with chronic HBV infection versus the A allele (OR 0.77; 95% CI 0.68, 0.88). When stratifying by type of study control, a significantly decreased risk was associated with CTLA4+49 variant genotypes (AG and GG) in both spontaneous recovery control group and healthy control group.

Conclusions: Findings of this meta-analysis suggest that A at position +49 of the CTLA4 gene may significantly increase the risk of persistent HBV infection, whereas G at position +49 may positively influence virus clearance.

Keywords: CTLA4; Chronic hepatitis B infection; HBV; cytotoxic T-lymphocyte associated protein 4; meta-analysis; single nucleotide polymorphism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • CTLA-4 Antigen / genetics*
  • CTLA-4 Antigen / immunology
  • Case-Control Studies
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / virology
  • Virus Replication

Substances

  • CTLA-4 Antigen