Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein-Related Measures

作者：Chu Audrey Y^*; Giulianini Franco; Barratt Bryan J; Ding Bo; Nyberg Fredrik; Mora Samia; Ridker Paul M; Chasman Daniel I

来源：Circulation-Cardiovascular Genetics, 2015, 8(5): 688-695.

DOI：10.1161/CIRCGENETICS.114.000962

• cholesterol
• genetics
• genome-wide association study
• lipoproteins
• LDL
• NMR spectroscopy
• rosuvastatin

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.

• 出版日期2015-10