Maarten Leusink1,2, N Charlotte Onland-Moret2, Paul I W de Bakker2,3, Anthonius de Boer1, Anke H Maitland-van der Zee1. 1. Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. 2. Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 3. Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
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.
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.
Authors: Marleen E Jansen; T Rigter; W Rodenburg; T M C Fleur; E J F Houwink; M Weda; Martina C Cornel Journal: Front Pharmacol Date: 2017-08-23 Impact factor: 5.810