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

✍ Scribed by Catherine J. Edwards-Smith; Julie R. Jonsson; David M. Purdie; Amolak Bansal; Claudia Shorthouse; Elizabeth E. Powell

Publisher: John Wiley and Sons
Year: 1999
Tongue: English
Weight: 85 KB
Volume: 30
Category: Article
ISSN: 0270-9139
DOI: 10.1002/hep.510300207

No coin nor oath required. For personal study only.

✦ Synopsis

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-␣). 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-␣ 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-␣ therapy. Patients who are genetically predisposed to high IL-10 production have a poor response to IFN-␣ and may benefit from additional treatment strategies designed to enhance a T-helper type 1 (Th1) response. (HEPATOLOGY 1999;30:526-530.

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