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

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 assoc...

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Published in:PloS one 2012-05, Vol.7 (5), p.e38240-e38240
Main Authors: Shiffman, Dov, Trompet, Stella, Louie, Judy Z, Rowland, Charles M, Catanese, Joseph J, Iakoubova, Olga A, Kirchgessner, Todd G, Westendorp, Rudi G J, de Craen, Anton J M, Slagboom, P Eline, Buckley, Brendan M, Stott, David J, Sattar, Naveed, Devlin, James J, Packard, Christopher J, Ford, Ian, Sacks, Frank M, Jukema, J Wouter
Format: Article
Language:English
Subjects:
Aged
Analysis
Antilipemic agents
Cardiovascular agents
Cardiovascular disease
Cardiovascular diseases
Cholesterol
Chromosomes
Coronary artery disease
Coronary Disease - drug therapy
Coronary Disease - genetics
Coronary Disease - prevention & control
Coronary heart disease
Disease control
Disease susceptibility
Female
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease - genetics
Genetic research
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Geriatrics
Health risks
Heart
Heart diseases
Homology
Humans
Low density lipoprotein
Male
Medicine
Middle Aged
Older people
Pharmacogenomics
Pharmacology
Polymorphism, Single Nucleotide
Pravastatin
Pravastatin - pharmacology
Pravastatin - therapeutic use
Prevention
Randomization
Risk
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Statins
Studies
Therapy
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cited_by cdi_FETCH-LOGICAL-c692t-9a4c510eedf669fb5546d5d0a01cdf8288ac85f1877f651a18f35e4d736c67823
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container_end_page e38240
container_issue 5
container_start_page e38240
container_title PloS one
container_volume 7
creator Shiffman, Dov
Trompet, Stella
Louie, Judy Z
Rowland, Charles M
Catanese, Joseph J
Iakoubova, Olga A
Kirchgessner, Todd G
Westendorp, Rudi G J
de Craen, Anton J M
Slagboom, P Eline
Buckley, Brendan M
Stott, David J
Sattar, Naveed
Devlin, James J
Packard, Christopher J
Ford, Ian
Sacks, Frank M
Jukema, J Wouter
description 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
doi_str_mv 10.1371/journal.pone.0038240
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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&lt;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 = 4.8 × 10(-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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0038240</identifier><identifier>PMID: 22666496</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Analysis ; Antilipemic agents ; Cardiovascular agents ; Cardiovascular disease ; Cardiovascular diseases ; Cholesterol ; Chromosomes ; Coronary artery disease ; Coronary Disease - drug therapy ; Coronary Disease - genetics ; Coronary Disease - prevention &amp; control ; Coronary heart disease ; Disease control ; Disease susceptibility ; Female ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genetic research ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Geriatrics ; Health risks ; Heart ; Heart diseases ; Homology ; Humans ; Low density lipoprotein ; Male ; Medicine ; Middle Aged ; Older people ; Pharmacogenomics ; Pharmacology ; Polymorphism, Single Nucleotide ; Pravastatin ; Pravastatin - pharmacology ; Pravastatin - therapeutic use ; Prevention ; Randomization ; Risk ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statins ; Studies ; Therapy</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e38240-e38240</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Shiffman et al. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiffman, Dov</au><au>Trompet, Stella</au><au>Louie, Judy Z</au><au>Rowland, Charles M</au><au>Catanese, Joseph J</au><au>Iakoubova, Olga A</au><au>Kirchgessner, Todd G</au><au>Westendorp, Rudi G J</au><au>de Craen, Anton J M</au><au>Slagboom, P Eline</au><au>Buckley, Brendan M</au><au>Stott, David J</au><au>Sattar, Naveed</au><au>Devlin, James J</au><au>Packard, Christopher J</au><au>Ford, Ian</au><au>Sacks, Frank M</au><au>Jukema, J Wouter</au><au>Schunkert, Heribert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-30</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e38240</spage><epage>e38240</epage><pages>e38240-e38240</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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&lt;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 = 4.8 × 10(-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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22666496</pmid><doi>10.1371/journal.pone.0038240</doi><tpages>e38240</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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source PMC (PubMed Central); Publicly Available Content (ProQuest)
subjects Aged
Analysis
Antilipemic agents
Cardiovascular agents
Cardiovascular disease
Cardiovascular diseases
Cholesterol
Chromosomes
Coronary artery disease
Coronary Disease - drug therapy
Coronary Disease - genetics
Coronary Disease - prevention & control
Coronary heart disease
Disease control
Disease susceptibility
Female
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease - genetics
Genetic research
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Geriatrics
Health risks
Heart
Heart diseases
Homology
Humans
Low density lipoprotein
Male
Medicine
Middle Aged
Older people
Pharmacogenomics
Pharmacology
Polymorphism, Single Nucleotide
Pravastatin
Pravastatin - pharmacology
Pravastatin - therapeutic use
Prevention
Randomization
Risk
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Statins
Studies
Therapy
title Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy
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