Bookmark..
Add to Browser
Go to Browser 
Study Report - GWAS of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C (HGVST374)| HGVbaseG2P identifier | HGVST374 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study name | GWAS of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C | ||||||||||||||||||||
| Phenotype(s) tested | Response to hepatitis C treatment |
||||||||||||||||||||
| Study design | Cases (response) with replication | ||||||||||||||||||||
| Genotype Platforms |
Affymetrix 621,220 | ||||||||||||||||||||
| 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). | ||||||||||||||||||||
| Submission information |
|
||||||||||||||||||||
| Cross-references |
NHGRI GWAS catalog study annotation for HGVST374 |
||||||||||||||||||||
| Background | Not supplied | ||||||||||||||||||||
| Objectives | Not supplied | ||||||||||||||||||||
| Key results | Not supplied | ||||||||||||||||||||
| Conclusions | Not supplied | ||||||||||||||||||||
| Reason for study size | Not supplied | ||||||||||||||||||||
| Study power | Not supplied | ||||||||||||||||||||
| Sources of bias | Not supplied | ||||||||||||||||||||
| Limitations | Not supplied | ||||||||||||||||||||
| Acknowledgements | Not supplied | ||||||||||||||||||||
| Other citations |
Hindorff LA, Sethupathy P, Junkins HA et al.
Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences U S A. 2009 May 27
Tanaka Y, Nishida N, Sugiyama M et al.
Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nature genetics 2009;41(10):1105-9 |
