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Interleukin‐10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa

Interleukin‐10 promoter polymorphism predicts initial response of chronic hepatitis C to... Serum levels of interleukin‐10 (IL‐10) are elevated in a proportion of patients with untreated chronic hepatitis C, and this may compromise the host immune response to the virus. The capacity for IL‐10 production varies according to the genetic composition of the IL‐10 locus. We examined the inheritance of 3 biallelic polymorphisms in the IL‐10 gene promoter in patients with chronic hepatitis C and their association with response to treatment with interferon alfa (IFN‐α). After adjusting for potential confounding variables, a highly significant relationship was found between inheritance of the IL‐10 promoter −592*A and −819*T alleles or the ATA haplotype and response to IFN‐α therapy (P = .016). Response to treatment was also associated with viral genotype 3a, a low viral load, and less fibrosis on liver biopsy. Following in vitro stimulation of peripheral blood mononuclear cells, the IL‐10 promoter haplotypes, GCC, ACC, and ATA, were associated with high, intermediate, and low IL‐10 production, respectively. These findings indicate that heterogeneity in the promoter region of the IL‐10 gene has a role in determining the initial response of chronic hepatitis C to IFN‐α therapy. Patients who are genetically predisposed to high IL‐10 production have a poor response to IFN‐α and may benefit from additional treatment strategies designed to enhance a T‐helper type 1 (Th1) response. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology Wiley

Interleukin‐10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa

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References (46)

Publisher
Wiley
Copyright
Copyright © 1999 American Association for the Study of Liver Diseases
ISSN
0270-9139
eISSN
1527-3350
DOI
10.1002/hep.510300207
pmid
10421663
Publisher site
See Article on Publisher Site

Abstract

Serum levels of interleukin‐10 (IL‐10) are elevated in a proportion of patients with untreated chronic hepatitis C, and this may compromise the host immune response to the virus. The capacity for IL‐10 production varies according to the genetic composition of the IL‐10 locus. We examined the inheritance of 3 biallelic polymorphisms in the IL‐10 gene promoter in patients with chronic hepatitis C and their association with response to treatment with interferon alfa (IFN‐α). After adjusting for potential confounding variables, a highly significant relationship was found between inheritance of the IL‐10 promoter −592*A and −819*T alleles or the ATA haplotype and response to IFN‐α therapy (P = .016). Response to treatment was also associated with viral genotype 3a, a low viral load, and less fibrosis on liver biopsy. Following in vitro stimulation of peripheral blood mononuclear cells, the IL‐10 promoter haplotypes, GCC, ACC, and ATA, were associated with high, intermediate, and low IL‐10 production, respectively. These findings indicate that heterogeneity in the promoter region of the IL‐10 gene has a role in determining the initial response of chronic hepatitis C to IFN‐α therapy. Patients who are genetically predisposed to high IL‐10 production have a poor response to IFN‐α and may benefit from additional treatment strategies designed to enhance a T‐helper type 1 (Th1) response.

Journal

HepatologyWiley

Published: Aug 1, 1999

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