Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection


Yee, LJ; Perez, KA; Tang, J; van Leeuwen, DJ; Kaslow, RA; (2003) Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection. The Journal of infectious diseases, 187 (8). pp. 1264-71. ISSN 0022-1899 DOI: https://doi.org/10.1086/374561

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Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA4) suppresses cytotoxic T lymphocyte activity. We examined the associations of CTLA4 single-nucleotide polymorphisms (SNPs) at promoter site -318 and exon-1 site 49 with clearance of hepatitis C virus (HCV) after treatment with combination interferon-alpha plus ribavirin (IFN-alpha+R) therapy in 79 white sustained responders (SRs) and 79 nonresponders (NRs). SRs had higher frequencies of 49G, alone (odds ratio [OR], 2.3; P=.042) and tightly linked with -318C in a haplotype (OR, 2.4; P=.030). Homozygosity for the -318C-49G haplotype was even more frequent among SRs (OR, 5.2; P=.049). Comparably strong associations persisted after multivariable analysis. Relationships were not seen with non-1 genotype viruses (OR, 0.93-1.25; P>.25). Virus load also declined more rapidly in carriers of both 49G (P=.0095) and the -318C-49G haplotype. CTLA4 49G in exon 1 alone and in a haplotype with -318C promoter is associated with sustained IFNalpha+R response in white patients with HCV genotype 1 infection.

Item Type: Article
Keywords: Adult, Antigens, Differentiation/*genetics/*immunology, Antiviral Agents/*therapeutic use, Female, Hepacivirus/*immunology, Hepatitis C, Chronic/*drug therapy/*genetics/immunology, Human, Interferon-alpha/*therapeutic use, Linkage (Genetics), Male, Pharmacogenetics, Polymorphism, Single Nucleotide/*genetics, Ribavirin/*therapeutic use, Support, Non-U.S. Gov't, Time Factors, Adult, Antigens, Differentiation, genetics, immunology, Antiviral Agents, therapeutic use, Female, Hepacivirus, immunology, Hepatitis C, Chronic, drug therapy, genetics, immunology, Human, Interferon-alpha, therapeutic use, Linkage (Genetics), Male, Pharmacogenetics, Polymorphism, Single Nucleotide, genetics, Ribavirin, therapeutic use, Support, Non-U.S. Gov't, Time Factors
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 12696006
Web of Science ID: 181972000012
URI: http://researchonline.lshtm.ac.uk/id/eprint/16066

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