期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 8, 期 5, 页码 688-695出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.114.000962
关键词
cholesterol; genetics; genome-wide association study; lipoproteins; LDL; NMR spectroscopy; rosuvastatin
资金
- AstraZeneca
- National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL117861]
- [T32HL757520]
Background Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. Methods and Results One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. Conclusions These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
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