Lipid-lowering response to statins is affected by CYP3A5 polymorphism.
Individuals expressing the polymorphic CYP3A5 enzyme might show a more than average efficiency in the metabolism of lovastatin, simvastatin and atorvastatin. We studied whether the expression of CYP3A5 is associated with an impaired lipid-lowering response to statins in 69 Caucasian patients. Lovastatin, simvastatin and atorvastatin were significantly less effective in CYP3A5 expressors than in non-expressors. The mean serum total cholesterol concentration at 1 year was 23% higher (P = 0.0014) and the mean serum low-density lipoprotein cholesterol concentration was 24% higher (P = 0.036) in subjects possessing the CYP3A5*1 allele (CYP3A5 expressors, n = 7) than in subjects homozygous for the CYP3A5*3 allele (non-expressors, n = 39). The mean percentage reduction in serum total cholesterol from baseline was significantly smaller in CYP3A5 expressors than in non-expressors (17% versus 31%, P = 0.026). No association between hypolipidemic efficacy and CYP3A5 polymorphism was observed among 23 subjects taking statins that are not dependent on CYP3A5 (fluvastatin, pravastatin). These findings suggest that CYP3A5 may be a genetic determinant of interindividual differences in response to certain statins.
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Kari T
KT
Kivistö
Mikko
M
Niemi
Elke
E
Schaeffeler
Kaisu
K
Pitkälä
Reijo
R
Tilvis
Martin F
MF
Fromm
Matthias
M
Schwab
Michel
M
Eichelbaum
Timo
T
Strandberg
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000494:pharmacology; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011758:Pyrroles / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A