Source:http://linkedlifedata.com/resource/pubmed/id/11230752
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2001-3-14
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pubmed:abstractText |
Host genetic factors have been reported to influence the natural history of hepatitis C virus (HCV) infection. We examined whether variation in interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha) genes would predict the likelihood of sustained response to antiviral therapy. Single nucleotide polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10 and TNF-alpha were determined by polymerase chain reaction (PCR)-based techniques. Their relationship to the outcome of antiviral therapy for chronic HCV infection was studied in 49 white patients who had a virologically sustained response (SR) and in 55 white nonresponders (NR) to a combination of interferon alfa-2b and ribavirin (IFN + R). Several IL-10 variants were more frequent among SRs compared with NRs. Carriage of the -592A or the -819T SNP was associated with SR (odds ratio [OR] = 2.2; P =.016). The -592A/A and the exclusively linked -819T/T genotypes were also associated with SR (OR = 16.6; P =.013 for either). The haplotype consisting of the 108-bp IL-10.R microsatellite and -3575T, -2763C, -1082A, -819T, -592A was also associated with SR (OR = 2.65; P =.01). Stratification for viral genotype, baseline viral RNA concentration, and histologic status identified homozygosity for the haplotype as the principal determinant: all 5 homozygous individuals achieved SR (OR(crude) = 13.7; P =.025; stratified ORs = 1.9-7.0), whereas heterozygotes differed only slightly from wild-type carriers. In contrast, TNF alleles defined by promoter sequences -238G/A and -308G/A were approximately equally distributed among SR and NR. In conclusion, homozygosity for -592A, -819T or the extended haplotype (108bp) - (-2575T) - (-2763C) - (-1082A) - (-819T) - (-592A) is associated with SR to IFN + R.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribavirin,
http://linkedlifedata.com/resource/pubmed/chemical/interferon alfa-2b
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0270-9139
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
708-12
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11230752-Alleles,
pubmed-meshheading:11230752-Antiviral Agents,
pubmed-meshheading:11230752-Drug Therapy, Combination,
pubmed-meshheading:11230752-Gene Frequency,
pubmed-meshheading:11230752-Genetic Variation,
pubmed-meshheading:11230752-Haplotypes,
pubmed-meshheading:11230752-Hepatitis C, Chronic,
pubmed-meshheading:11230752-Heterozygote,
pubmed-meshheading:11230752-Homozygote,
pubmed-meshheading:11230752-Humans,
pubmed-meshheading:11230752-Interferon-alpha,
pubmed-meshheading:11230752-Interleukin-10,
pubmed-meshheading:11230752-Polymorphism, Genetic,
pubmed-meshheading:11230752-Prognosis,
pubmed-meshheading:11230752-Recombinant Proteins,
pubmed-meshheading:11230752-Ribavirin
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pubmed:year |
2001
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pubmed:articleTitle |
Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection.
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pubmed:affiliation |
Program in Epidemiology of Infection and Immunity, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 35294-0022, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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