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-α plus riba...

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Bibliographic Details
Published in:The Journal of infectious diseases 2003-04, Vol.187 (8), p.1264-1271
Main Authors: Yee, Leland J, Perez, Kevin A, Tang, Jianming, Leeuwen, Dirk J. van, Kaslow, Richard A
Format: Article
Language:English
Subjects:
Abatacept
Adult
Alleles
Antigens, CD
Antigens, Differentiation - genetics
Antigens, Differentiation - immunology
Antiviral Agents - therapeutic use
Biological and medical sciences
Chronic hepatitis
CTL protein
CTLA-4 Antigen
Female
Genetic Linkage
Genotypes
Haplotypes
Hepacivirus
Hepacivirus - immunology
Hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - immunology
Human viral diseases
Humans
Immunoconjugates
Infections
Infectious diseases
Interferon-alpha - therapeutic use
Malaria
Male
Medical sciences
Pharmacogenetics
Polymorphism, Single Nucleotide - genetics
Ribavirin - therapeutic use
Schistosomiasis
T lymphocytes
Time Factors
Viral diseases
Viral hepatitis
Viruses
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Summary: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-α plus ribavirin (IFN-α+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 IFNα+R response in white patients with HCV genotype 1 infection
ISSN:0022-1899
1537-6613
DOI:10.1086/374561