title: Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection.
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.
authors.affiliation: Program in Epidemiology of Infection and Immunity, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Leland J
authors.initials: LJ
authors.lastname: Yee
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Perez
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Leeuwen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D005260:Female; D008040:Genetic Linkage; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D016898:Interferon-alpha; D012254:Ribavirin; D000069594:Abatacept