Statin pharmacogenomics: what have we learned, and what remains unanswered?

被引:7
作者
Kajinami, K
Okabayashi, M
Sato, R
Polisecki, E
Schaefer, EJ
机构
[1] Kanazawa Med Univ, Dept Cardiol, Uchinada, Ishikawa 9200293, Japan
[2] Tufts Univ, Cardiovasc Res & Lipid Metab Labs, Boston, MA 02111 USA
关键词
HDL cholesterol; HMG-CoA reductase inhibitor (statin); LDL cholesterol; pharmacogenomics (pharmacogenetics);
D O I
10.1097/01.mol.0000191914.54439.b7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Purpose of review Statins are widely prescribed and are established as first-line therapy for the primary and secondary prevention of coronary heart disease. Response to treatment varies considerably from person to person; however, inherited traits (genetic variability) may play a central role in this inter-individual variation. The purpose of this review is to summarize recent progress in the research for exploring genetic determinants of clinical efficacy and safety of statin therapy. Recent findings In addition to 41 previous studies of 19 genes, the results of 17 pharmacogenomic studies investigating the relationship between common genetic variants and response to statin 1 therapy in terms of lipid responses, clinical outcomes, and adverse events have been reported since January 2004 15 candidate genes related to pharmacodynamics and three to pharmacokinetics of statins. These reported data suggest that genetic variations influencing intestinal cholesterol absorption, cholesterol production, and lipoprotein catabolism may all play a role in modulating responsiveness, as well as genes involved in drug metabolism of statins. They also suggest that combined analysis of multiple variants in several genes, all of which have possible functional relations, is more likely to give significant results, especially when being performed with a larger number of participants. Summary Pharmacogenomic studies of statin therapy will provide a better picture as to who is most likely and least likely to benefit from treatment, which results in more individualized management of coronary artery disease.
引用
收藏
页码:606 / 613
页数:8
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