Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

被引:82
作者
Kaddurah-Daouk, Rima [1 ]
Baillie, Rebecca A. [2 ]
Zhu, Hongjie [4 ,5 ]
Zeng, Zhao-Bang [4 ,5 ]
Wiest, Michelle M. [3 ]
Nguyen, Uyen Thao [3 ]
Watkins, Steven M. [3 ]
Krauss, Ronald M. [6 ]
机构
[1] Duke Univ, Med Ctr, Durham, NC 27710 USA
[2] Rosa & Co LLC, San Carlos, CA 94070 USA
[3] Lip Technol Tethys Biosci, W Sacramento, CA 95691 USA
[4] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA
[5] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA
[6] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA
关键词
Cardiovascular disease; Lipidomics; Metabolomics; Pharmacogenomics; Pharmacometabolomics; Simvastatin; FATTY-ACID-COMPOSITION; CORONARY-ARTERY-DISEASE; LOW-DENSITY LIPOPROTEIN; C-REACTIVE PROTEIN; RANDOMIZED-TRIALS; PLASMA; STATINS; ESTERS; CELLS; HYPERCHOLESTEROLEMIA;
D O I
10.1007/s11306-010-0207-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins.
引用
收藏
页码:191 / 201
页数:11
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