Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

1. Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Authors
Tanaka Y¹
(1 author)

ORCIDs linked to this article

Tanaka Y | 0000-0002-2473-6966

Nature Genetics, 13 Sep 2009, 41(10):1105-1109
https://doi.org/10.1038/ng.449 PMID: 19749757

A comment on this article appears in "Predicting response to pegylated interferon/ribavirin-based therapy in genotype 1 chronic hepatitis C patients: results of 3 independent genome-wide association studies." Gastroenterology. 2010 Apr;138(4):1622-4. A comment on this article appears in "Pharmacogenetics of hepatitis C therapy." Pharmacogenomics. 2010 Feb;11(2):135-9. A comment on this article appears in "Interferon-alfa, interferon-lambda and hepatitis C." Nat Genet. 2009 Oct;41(10):1048-50.

Abstract

The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).

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SNPs (Showing 6 of 6)

(2 citations) dbSNP - rs12980275
(1 citation) dbSNP - rs8103142
(1 citation) dbSNP - rs8099917
(1 citation) dbSNP - rs8105790
(1 citation) dbSNP - rs28416813
(1 citation) dbSNP - rs11881222

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Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

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