Seventeen years of statin pharmacogenetics: a systematic review
We evaluated the evidence of pharmacogenetic associations with statins in a systematic review. Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events. In candidate gene studies, 141 lo...
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| Veröffentlicht in: | Pharmacogenomics 2016-01, Vol.17 (2), p.163-180 |
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| creator | Leusink, Maarten Onland-Moret, N Charlotte de Bakker, Paul IW de Boer, Anthonius Maitland-van der Zee, Anke H |
| description | We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.
Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.
In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in
,
,
,
and
at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.
Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice. |
| doi_str_mv | 10.2217/pgs.15.158 |
| format | Article |
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Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.
In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in
,
,
,
and
at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.
Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.</description><identifier>ISSN: 1462-2416</identifier><identifier>EISSN: 1744-8042</identifier><identifier>DOI: 10.2217/pgs.15.158</identifier><identifier>PMID: 26670324</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Adaptor Proteins, Vesicular Transport - genetics ; Alzheimer's disease ; Apolipoprotein E ; Apolipoproteins E - genetics ; Atherosclerosis ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters - genetics ; candidate gene studies ; Cardiovascular diseases ; Cardiovascular Diseases - prevention & control ; Cholesterol ; Cholesterol, LDL - blood ; Ethnicity ; Genes ; Genetic Loci ; Genetic screening ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics ; LDL cholesterol ; Lipid Metabolism - genetics ; Lipids ; Lipoprotein(a) - genetics ; Lipoproteins ; Low density lipoprotein ; Neoplasm Proteins - genetics ; Organic Anion Transporters - genetics ; Pharmacogenetics ; Polymorphism, Single Nucleotide ; Principal components analysis ; Quality ; review ; Single-nucleotide polymorphism ; Solute Carrier Organic Anion Transporter Family Member 1b1 ; Statins ; Stroke ; Studies</subject><ispartof>Pharmacogenomics, 2016-01, Vol.17 (2), p.163-180</ispartof><rights>Future Medicine Ltd</rights><rights>Copyright Future Medicine Ltd Jan 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-ebc83235aa8c3cc9437fbe5d9526fff93841ee91b8bba436ccc5284217ec6f733</citedby><cites>FETCH-LOGICAL-c362t-ebc83235aa8c3cc9437fbe5d9526fff93841ee91b8bba436ccc5284217ec6f733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4022,27922,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26670324$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leusink, Maarten</creatorcontrib><creatorcontrib>Onland-Moret, N Charlotte</creatorcontrib><creatorcontrib>de Bakker, Paul IW</creatorcontrib><creatorcontrib>de Boer, Anthonius</creatorcontrib><creatorcontrib>Maitland-van der Zee, Anke H</creatorcontrib><title>Seventeen years of statin pharmacogenetics: a systematic review</title><title>Pharmacogenomics</title><addtitle>Pharmacogenomics</addtitle><description>We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.
Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.
In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in
,
,
,
and
at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.
Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.</description><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Alzheimer's disease</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - genetics</subject><subject>Atherosclerosis</subject><subject>ATP Binding Cassette Transporter, Sub-Family G, Member 2</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>candidate gene studies</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL - blood</subject><subject>Ethnicity</subject><subject>Genes</subject><subject>Genetic Loci</subject><subject>Genetic screening</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</subject><subject>LDL cholesterol</subject><subject>Lipid Metabolism - genetics</subject><subject>Lipids</subject><subject>Lipoprotein(a) - genetics</subject><subject>Lipoproteins</subject><subject>Low density lipoprotein</subject><subject>Neoplasm Proteins - genetics</subject><subject>Organic Anion Transporters - genetics</subject><subject>Pharmacogenetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Principal components analysis</subject><subject>Quality</subject><subject>review</subject><subject>Single-nucleotide polymorphism</subject><subject>Solute Carrier Organic Anion Transporter Family Member 1b1</subject><subject>Statins</subject><subject>Stroke</subject><subject>Studies</subject><issn>1462-2416</issn><issn>1744-8042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkE1Lw0AQhhdRbP24-AMk4EWE1P1O4kWk-AUFD-p52Uxna0qT1N2k0n_vllYPIgzMDPPMy8xLyBmjI85Zdr2chRFTMfI9MmSZlGlOJd-PtdQ85ZLpATkKYU4pZ1rSQzLgWmdUcDkkt6-4wqZDbJI1Wh-S1iWhs13VJMsP62sL7Qwb7CoIN4lNwjp0WMcxJB5XFX6dkANnFwFPd_mYvD_cv42f0snL4_P4bpKC0LxLsYRccKGszUEAFFJkrkQ1LRTXzrlC5JIhFqzMy9JKoQFA8VzG7xC0y4Q4Jpdb3aVvP3sMnamrALhY2AbbPhiWKVYUSggV0Ys_6LztfROvM1xwXfCM0g11taXAtyF4dGbpq9r6tWHUbGw10VbDVIw8wuc7yb6scfqL_vgYAb0FXN_1HgNU2ACabRc3Kqga_E_5G1vphYk</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Leusink, Maarten</creator><creator>Onland-Moret, N Charlotte</creator><creator>de Bakker, Paul IW</creator><creator>de Boer, Anthonius</creator><creator>Maitland-van der Zee, Anke H</creator><general>Future Medicine Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>EHMNL</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160101</creationdate><title>Seventeen years of statin pharmacogenetics: a systematic review</title><author>Leusink, Maarten ; Onland-Moret, N Charlotte ; de Bakker, Paul IW ; de Boer, Anthonius ; Maitland-van der Zee, Anke H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-ebc83235aa8c3cc9437fbe5d9526fff93841ee91b8bba436ccc5284217ec6f733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adaptor Proteins, Vesicular Transport - genetics</topic><topic>Alzheimer's disease</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins E - genetics</topic><topic>Atherosclerosis</topic><topic>ATP Binding Cassette Transporter, Sub-Family G, Member 2</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>candidate gene studies</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cholesterol</topic><topic>Cholesterol, LDL - blood</topic><topic>Ethnicity</topic><topic>Genes</topic><topic>Genetic Loci</topic><topic>Genetic screening</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</topic><topic>LDL cholesterol</topic><topic>Lipid Metabolism - genetics</topic><topic>Lipids</topic><topic>Lipoprotein(a) - genetics</topic><topic>Lipoproteins</topic><topic>Low density lipoprotein</topic><topic>Neoplasm Proteins - genetics</topic><topic>Organic Anion Transporters - genetics</topic><topic>Pharmacogenetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Principal components analysis</topic><topic>Quality</topic><topic>review</topic><topic>Single-nucleotide polymorphism</topic><topic>Solute Carrier Organic Anion Transporter Family Member 1b1</topic><topic>Statins</topic><topic>Stroke</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leusink, Maarten</creatorcontrib><creatorcontrib>Onland-Moret, N Charlotte</creatorcontrib><creatorcontrib>de Bakker, Paul IW</creatorcontrib><creatorcontrib>de Boer, Anthonius</creatorcontrib><creatorcontrib>Maitland-van der Zee, Anke H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>UK & Ireland Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacogenomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leusink, Maarten</au><au>Onland-Moret, N Charlotte</au><au>de Bakker, Paul IW</au><au>de Boer, Anthonius</au><au>Maitland-van der Zee, Anke H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Seventeen years of statin pharmacogenetics: a systematic review</atitle><jtitle>Pharmacogenomics</jtitle><addtitle>Pharmacogenomics</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>17</volume><issue>2</issue><spage>163</spage><epage>180</epage><pages>163-180</pages><issn>1462-2416</issn><eissn>1744-8042</eissn><abstract>We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.
Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.
In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in
,
,
,
and
at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.
Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>26670324</pmid><doi>10.2217/pgs.15.158</doi><tpages>18</tpages></addata></record> |
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| ispartof | Pharmacogenomics, 2016-01, Vol.17 (2), p.163-180 |
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| language | eng |
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| subjects | Adaptor Proteins, Vesicular Transport - genetics Alzheimer's disease Apolipoprotein E Apolipoproteins E - genetics Atherosclerosis ATP Binding Cassette Transporter, Sub-Family G, Member 2 ATP-Binding Cassette Transporters - genetics candidate gene studies Cardiovascular diseases Cardiovascular Diseases - prevention & control Cholesterol Cholesterol, LDL - blood Ethnicity Genes Genetic Loci Genetic screening Genome-wide association studies Genome-Wide Association Study Genomes Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics LDL cholesterol Lipid Metabolism - genetics Lipids Lipoprotein(a) - genetics Lipoproteins Low density lipoprotein Neoplasm Proteins - genetics Organic Anion Transporters - genetics Pharmacogenetics Polymorphism, Single Nucleotide Principal components analysis Quality review Single-nucleotide polymorphism Solute Carrier Organic Anion Transporter Family Member 1b1 Statins Stroke Studies |
| title | Seventeen years of statin pharmacogenetics: a systematic review |
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