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Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment
- Smit, Roelof AJ;
- Postmus, Iris;
- Trompet, Stella;
- Barnes, Michael R;
- Warren, Helen;
- Arsenault, Benoit J;
- Chasman, Daniel I;
- Cupples, L Adrienne;
- Hitman, Graham A;
- Krauss, Ronald M;
- Li, Xiaohui;
- Psaty, Bruce M;
- Stein, Charles M;
- Rotter, Jerome I;
- Jukema, J Wouter
Published Web Location
https://doi.org/10.2217/pgs-2016-0091Abstract
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.
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