Seventeen years of statin pharmacogenetics: a systematic review

Maarten Leusink; N Charlotte Onland-Moret; Paul de Bakker; Anthonius de Boer; Anke H Maitland-van der Zee

doi:10.2217/pgs.15.158

Seventeen years of statin pharmacogenetics: a systematic review

Maarten Leusink
, N Charlotte Onland-Moret
, Paul de Bakker
, Anthonius de Boer
, Anke H Maitland-van der Zee

Research output: Contribution to journal › Literature review › peer-review

Abstract

AIM: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.

METHODS: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.

RESULTS: 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 APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.

CONCLUSION: 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.

Original language	English
Pages (from-to)	163-180
Number of pages	18
Journal	Pharmacogenomics
Volume	17
Issue number	2
DOIs	https://doi.org/10.2217/pgs.15.158
Publication status	Published - 2016

Keywords

candidate gene studies
genome-wide association studies
LDL cholesterol
pharmacogenetics
review
statins

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10.2217/pgs.15.158

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title = "Seventeen years of statin pharmacogenetics: a systematic review",

abstract = "AIM: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.METHODS: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.RESULTS: 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 APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.CONCLUSION: 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.",

keywords = "candidate gene studies, genome-wide association studies, LDL cholesterol, pharmacogenetics, review, statins",

author = "Maarten Leusink and Onland-Moret, \{N Charlotte\} and \{de Bakker\}, Paul and \{de Boer\}, Anthonius and \{Maitland-van der Zee\}, \{Anke H\}",

year = "2016",

doi = "10.2217/pgs.15.158",

language = "English",

volume = "17",

pages = "163--180",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "2",

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TY - JOUR

T1 - Seventeen years of statin pharmacogenetics

T2 - a systematic review

AU - Leusink, Maarten

AU - Onland-Moret, N Charlotte

AU - de Bakker, Paul

AU - de Boer, Anthonius

AU - Maitland-van der Zee, Anke H

PY - 2016

Y1 - 2016

N2 - AIM: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.METHODS: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.RESULTS: 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 APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.CONCLUSION: 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.

AB - AIM: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.METHODS: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.RESULTS: 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 APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.CONCLUSION: 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.

KW - candidate gene studies

KW - genome-wide association studies

KW - LDL cholesterol

KW - pharmacogenetics

KW - review

KW - statins

U2 - 10.2217/pgs.15.158

DO - 10.2217/pgs.15.158

M3 - Literature review

C2 - 26670324

SN - 1462-2416

VL - 17

SP - 163

EP - 180

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 2

ER -

Seventeen years of statin pharmacogenetics: a systematic review

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Keywords

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