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


RESULTS
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 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.


CONCLUSIONS
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.
Kajinami
Kouji
K
Department of Cardiology, Kanazawa Medical University, Uchinada, Japan. kajinami@kanazawa-med.ac.jp
Okabayashi
Mizuho
M
Sato
Ryoko
R
Polisecki
Eliana
E
Schaefer
Ernst J
EJ
D001711:Biotransformation; D003327:Coronary Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D015894:Genome, Human / Q000502:physiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors