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Meta-Analysis
. 2016 Apr;17(6):583-91.
doi: 10.2217/pgs.16.8. Epub 2016 Apr 5.

A Genetic Risk Score Is Associated With Statin-Induced Low-Density Lipoprotein Cholesterol Lowering

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Free PMC article
Meta-Analysis

A Genetic Risk Score Is Associated With Statin-Induced Low-Density Lipoprotein Cholesterol Lowering

Maarten Leusink et al. Pharmacogenomics. .
Free PMC article

Abstract

Aim: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome.

Patients & methods: In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE.

Results: No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10(-4)).

Conclusion: The GRS was associated with statin response, but the small effect size (˜2% of the average low-density lipoprotein cholesterol reduction) limits applicability.

Keywords: pharmacogenetics cholesterol; risk score; statin therapy.

Conflict of interest statement

Financial & competing interests disclosure

This work was supported by: ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research; ASCOT: This work was supported by Pfizer, New York, NY, USA, for the ASCOT study and the collection of the ASCOT DNA repository; by Servier Research Group, Paris, France; and by Leo Laboratories, Copenhagen, Denmark. We thank all ASCOT trial participants, physicians, nurses and practices in the participating countries for their important contribution to the study. We thank the Centre National de Genotypage for genotyping. This work forms part of the research themes contributing to the translational research portfolio for the NIHR Barts Cardiovascular Biomedical Research Unit (Warren, Munroe and Caulfield); CARe: wishes to acknowledge the support of the National Heart, Lung and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research (NHLBI contract number HHSN268200960009C); FHS: The Framingham Heart Study research included in this study is funded by NIH grant/contract N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321, and by the NIH Intramural Research Program; JUPITER: The Jupiter study and genotyping of the study participants was funded by AstraZeneca; MESA: MESA was supported by the following: University of Washington (N01-HC-95159), University of California, Los Angeles (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205) and University of Virginia. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org; WHII: We thank all participating women and men in the Whitehall II Study, as well as all Whitehall II research scientists, study and data managers and clinical and administrative staff who make the study possible. The Whitehall II study has been supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (HL36310), US, NIH: National Institute on Aging (AG13196), US, NIH; Agency for Health Care Policy Research (HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. A.D.H. holds a British Heart Foundation Senior Research Fellowship. A clinical fellowship from The Netherlands Organisation for Health Research and Development (ZonMw grant 90700342 to FW Asselbergs); Utrecht University (‘Epidemiology Program’ to M Leusink).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Forest plot for the association between the genetic risk score and low-density lipoprotein cholesterol reduction.
Analyses were adjusted for baseline LDLc values. LDLc: Low-density lipoprotein cholesterol.

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