Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection.
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.
Yee
Leland J
LJ
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.
Perez
Kevin A
KA
Tang
Jianming
J
van Leeuwen
Dirk J
DJ
Kaslow
Richard A
RA
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
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