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Journal of Virology, October 2004, p. 11258-11262, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11258-11262.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytotoxic T-Lymphocyte Antigen 4 Gene and Recovery from Hepatitis B Virus Infection

Department of Medicine,¹ Department of Epidemiology, Johns Hopkins Medical Institutions, Baltimore,⁴ Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland,⁶ Department of Epidemiology, University of Alabama, Birmingham, Alabama,² Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio,³ New York Academy of Medicine, New York, New York⁵

Received 23 March 2004/ Accepted 15 June 2004

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. We hypothesized that single-nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor of the T-cell response to hepatitis B virus (HBV) infection, thus influencing viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from which all frequent haplotypes can be determined, using a large, matched panel of subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for each subject using PHASE software. The haplotype distribution differed between those with viral persistence and those with clearance. Two haplotypes were associated with clearance of HBV infection, which was most likely due to associations with the SNPs –1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a decreased T-cell response (+6230A), was associated with viral persistence (OR = 1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV infection, which is consistent with the emerging role of T regulatory cells in the pathogenesis of disease.

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