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The Effect of Apolipoprotein E Polymorphism on the Response to Lipid-Lowering Treatment With Atorvastatin or Fenofibrate

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece

Evangelos N. Liberopoulos, MD, FASA, FRSH

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece

Anna I. Kakafika, MD

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece

George A. Miltiadous, MD

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece

Marios Cariolou, PhD

Molecular Genetics Department B-DNA Identification Laboratory, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

Emmanuel S. Ganotakis, MD, FASA

Department of Internal Medicine, Medical School, University of Crete, Heraklion, Greece

Dimitri P. Mikhailidis, MD, FASA, FRCP, FRCPath

Department of Clinical Biochemistry, Vascular Disease Prevention Clinics, Royal Free Hospital, Royal Free and University College Medical School, London, UK

Moses S. Elisaf, MD, FRSH, FASA, FISA

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece, egepi{at}cc.uoi.gr

Although the effect of apolipoprotein E gene polymorphism on the response to treatment with statins has been studied, the results are conflicting. Moreover, little is known about the possible effect of apolipoprotein E alleles on the response to treatment with fibrates. The purpose of this study was to evaluate the effect of apolipoprotein E polymorphism on lipid-lowering response to treatment with atorvastatin and fenofibrate in patients with different types of dyslipidemia. The study population included 136 patients with heterozygous familial hypercholesterolemia (type IIA dyslipidemia) treated with atorvastatin (20 mg/day) and 136 patients with either primary hypertriglyceridemia (type IV dyslipidemia) or mixed hyperlipidemia (type IIB dyslipidemia) treated with micronized fenofibrate (200 mg/day). Overall, no significant associations were detected between apolipoprotein E genotype and response to treatment with atorvastatin. In patients treated with fenofibrate, significant associations were noted between apolipoprotein E genotype and changes in apolipoprotein B, apolipoprotein E and triglyceride levels. Specifically, in apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 individuals, apolipoprotein B reductions were 22%, 17%, and 8%, respectively (P = .003); apolipoprotein E reductions were 45%, 20%, and 15%, respectively (P = .006); whereas triglyceride reductions reached 53%, 36%, and 33%, respectively (P = .033). In conclusion, apolipoprotein E genotype had no significant effect on the response to treatment with atorvastatin in patients with heterozygous familial hypercholesterolemia, but in patients with primary hypertriglyceridemia or mixed hyperlipidemia, there was a clear association between apolipoprotein E genotype and response to treatment with fenofibrate.

Key Words: atorvastatin • fenofibrate • apolipoprotein E • genotype • low-density lipoprotein cholesterol • triglycerides

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 3, 211-221 (2006)
DOI: 10.1177/1074248406293732


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