Genetic polymorphisms: importance for response to HMG-CoA reductase inhibitors.
Coronary artery disease is among the leading causes of death worldwide. Clinical trials show a protective effect of statins against the sequelae of coronary artery disease. The mean risk reductions for subjects using statins compared with placebo found in these trials is about 30%. These are average reductions for all patients included in the trials. Important factors in interpreting the variability in the outcome of drug therapy include the patient's health profile, prognosis, disease severity, quality of drug prescribing, compliance with prescribed pharmacotherapy and the genetic profile of the patient. This review aims to give an overview of the known polymorphisms (Cholesteryl Ester Transfer Protein polymorphism, Stromelysin-1 polymorphism, -455G/A and TaqI polymorphisms of the beta-fibrinogen gene, apoE4, Asp(9)Asn mutation in the lipoprotein lipase gene, the -514 CT polymorphism in the hepatic lipase gene and the ACE deletion type gene) that have an influence on the effects of statins in the general population. The expectation is that in the future a subject's genotype may determine whether he will be treated with statins or not. Determining the genotype will not deny therapy to a subject, but will help in deciding the therapy that will suit the patient best.
Maitland-van der Zee
Anke Hilse
AH
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, P.O. Box 80082, The Netherlands. a.h.maitland-vanderzee@pharm.uu.nl
Klungel
Olaf H
OH
Stricker
Bruno H Ch
BH
Monique Verschuren
W M
WM
Kastelein
John J P
JJ
Leufkens
Hubertus G M
HG
de Boer
Anthonius
A
D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000188:drug therapy / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D003362:Cost-Benefit Analysis; D005340:Fibrinogen / Q000235:genetics; D006023:Glycoproteins; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008049:Lipase / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005340:Fibrinogen; D008049:Lipase; D008071:Lipoprotein Lipase; D007703:Peptidyl-Dipeptidase A; D019278:Matrix Metalloproteinase 3