Genome-wide study of gene variants associated with differential cardiovascular event reduction by Pravastatin therapy

Shiffman, D. et al. (2012) Genome-wide study of gene variants associated with differential cardiovascular event reduction by Pravastatin therapy. PLoS ONE, 7(5), e38240. (doi: 10.1371/journal.pone.0038240) (PMID:22666496) (PMCID:PMC3364212)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0038240

Abstract

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P < 0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8x10(-7)). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Ford, Professor Ian and Packard, Professor Chris
Authors: Shiffman, D., Trompet, S., Louie, J.Z., Rowland, C.M., Catanese, J.J., Iakoubova, O.A., Kirchgessner, T.G., Westendorp, R.G.J., de Craen, A.J.M., Slagboom, P.E., Buckley, B.M., Stott, D., Devlin, J.J., Packard, C., Ford, I., Sacks, F.M., and Jukema, J.W.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:PLoS ONE
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:30 March 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(5):e38240
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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