Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment

被引：11

作者：

Smit, Roelof A. J. ^{[1
,2
]}

Postmus, Iris ^{[2
]}

Trompet, Stella ^{[1
,2
]}

Barnes, Michael R. ^{[3
,4
]}

Warren, Helen ^{[3
,4
]}

Arsenault, Benoit J. ^{[5
]}

Chasman, Daniel I. ^{[6
,7
]}

Cupples, L. Adrienne ^{[8
,9
]}

Hitman, Graham A. ^{[10
]}

Krauss, Ronald M. ^{[11
]}

Li, Xiaohui ^{[12
]}

Psaty, Bruce M. ^{[13
,14
,15
,16
]}

Stein, Charles M. ^{[17
,18
]}

Rotter, Jerome I. ^{[12
]}

Jukema, J. Wouter ^{[1
,19
,20
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands

[3] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England

[4] Queen Mary Univ London, Barts & London Sch Med, NIHR Barts Cardiovasc Biomed Res Unit, London EC1M 6BQ, England

[5] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada

[6] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[7] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA

[8] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[9] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[10] Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England

[11] Childrens Hosp Oakland, Res Inst, Dept Atherosclerosis Res, Oakland, CA 94609 USA

[12] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA

[13] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[14] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA

[15] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA

[16] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA

[17] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA

[18] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA

[19] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands

[20] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands

来源：

PHARMACOGENOMICS | 2016年 / 17卷 / 15期

关键词：

MR-Egger; pharmacogenetics; statin therapy; MENDELIAN RANDOMIZATION; LDL-CHOLESTEROL; HEART-DISEASE; NPC1L1; METAANALYSIS; EZETIMIBE; THERAPY; BIAS;

D O I：

10.2217/pgs-2016-0091

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aims: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response. Methods: We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia. Results: Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels. Conclusion: Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.

引用

页码：1621 / 1628

页数：8

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