ORIGINAL ARTICLESLipid-lowering response to statins is affected by CYP3A5 polymorphismKivistö, Kari Ta; Niemi, Mikkoa; Schaeffeler, Elkea; Pitkälä, Kaisub; Tilvis, Reijob; Fromm, Martin Fa; Schwab, Matthiasa; Eichelbaum, Michela; Strandberg, TimobAuthor Information aDr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and bDepartment of Medicine, Geriatric Clinic, University of Helsinki, Helsinki, Finland. Sponsorship: This work was supported by grants from the Robert-Bosch Foundation (Stuttgart, Germany), the Academy of Finland and the Helsinki University Central Hospital (Helsinki, Finland). M. Niemi is supported by a fellowship from the Alexander von Humboldt Foundation (Bonn, Germany). Correspondence and requests for reprints to: Kari Kivistö, Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, DE-70376 Stuttgart, Germany. Tel: +49 711 8101 3754; fax: +49 711 859 295; e-mail: [email protected] Received 8 April 2004 Accepted 12 May 2004 Pharmacogenetics: August 2004 - Volume 14 - Issue 8 - p 523-525 doi: 10.1097/01.fpc.0000114762.78957.a5 Buy Metrics Abstract 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. © 2004 Lippincott Williams & Wilkins, Inc.