The effect of apolipoprotein E polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate

被引:34
作者
Christidis, Dimitrios S.
Liberopoulos, Evangelos N.
Kakafika, Anna I.
Miltiadous, George A.
Cariolou, Marios
Ganotakis, Emmanuel S.
Mikhailidis, Dimitri P.
Elisaf, Moses S. [1 ]
机构
[1] Univ Ioannina, Dept Internal Med, Sch Med, GR-45110 Ioannina, Greece
[2] Cyprus Inst Neurol & Genet, Dept Mol Genet, B DNA Identificat Lab, Nicosia, Cyprus
[3] Univ Crete, Sch Med, Dept Internal Med, Iraklion, Greece
[4] UCL Royal Free & Univ Coll, Sch Med, Royal Free Hosp, Dept Clin Biochem,Vasc Dis Prevent Clin, London, England
关键词
atorvastatin; fenofibrate; apolipoprotein E; genotype; low-density lipoprotein cholesterol; triglycerides;
D O I
10.1177/1074248406293732
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 hypercholesterolernia (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 hyperlipidernia, there was a clear association between apolipoprotein E genotype and response to treatment with fenofibrate.
引用
收藏
页码:211 / 221
页数:11
相关论文
共 58 条
[1]   Evaluation of methods for the measurement of low-density lipoprotein cholesterol [J].
Bairaktari, ET ;
Seferiadis, KI ;
Elisaf, MS .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2005, 10 (01) :45-54
[2]   Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy [J].
Ballantyne, CM ;
Herd, JA ;
Stein, EA ;
Ferlic, LL ;
Dunn, JK ;
Gotto, AM ;
Marian, AJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 36 (05) :1572-1578
[3]   APOLIPOPROTEIN-E PHENOTYPES IN FAMILIAL HYPERCHOLESTEROLEMIA - IMPORTANCE FOR EXPRESSION OF DISEASE AND RESPONSE TO THERAPY [J].
BERGLUND, L ;
WIKLUND, O ;
EGGERTSEN, G ;
OLOFSSON, SO ;
ERIKSSON, M ;
LINDEN, T ;
BONDJERS, G ;
ANGELIN, B .
JOURNAL OF INTERNAL MEDICINE, 1993, 233 (02) :173-178
[4]   Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia [J].
Bilz, S ;
Wagner, S ;
Schmitz, M ;
Bedynek, A ;
Keller, U ;
Demant, T .
JOURNAL OF LIPID RESEARCH, 2004, 45 (01) :174-185
[5]   Effect of apolipoprotein E, peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients [J].
Brisson, D ;
Ledoux, K ;
Bossé, Y ;
St-Pierre, J ;
Julien, P ;
Perron, P ;
Hudson, TJ ;
Vohl, MC ;
Gaudet, D .
PHARMACOGENETICS, 2002, 12 (04) :313-320
[6]   THE RESPONSE TO LOVASTATIN TREATMENT IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IS MODULATED BY APOLIPOPROTEIN-E POLYMORPHISM [J].
CARMENA, R ;
ROEDERER, G ;
MAILLOUX, H ;
LUSSIERCACAN, S ;
DAVIGNON, J .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1993, 42 (07) :895-901
[7]   Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population:: Influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol [J].
Chaves, FJ ;
Real, JT ;
García-García, AB ;
Civera, M ;
Armengod, ME ;
Ascaso, JF ;
Carmena, R .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (10) :4926-4932
[8]   Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) [J].
Cleeman, JI ;
Grundy, SM ;
Becker, D ;
Clark, LT ;
Cooper, RS ;
Denke, MA ;
Howard, WJ ;
Hunninghake, DB ;
Illingworth, DR ;
Luepker, RV ;
McBride, P ;
McKenney, JM ;
Pasternak, RC ;
Stone, NJ ;
Van Horn, L ;
Brewer, HB ;
Ernst, ND ;
Gordon, D ;
Levy, D ;
Rifkind, B ;
Rossouw, JE ;
Savage, P ;
Haffner, SM ;
Orloff, DG ;
Proschan, MA ;
Schwartz, JS ;
Sempos, CT ;
Shero, ST ;
Murray, EZ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (19) :2486-2497
[9]   Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia [J].
Couture, P ;
Brun, LD ;
Szots, F ;
Lelièvre, M ;
Gaudet, D ;
Després, JP ;
Simard, J ;
Lupien, PJ ;
Gagné, C .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (06) :1007-1012
[10]  
DEKNIJFF P, 1990, ATHEROSCLEROSIS, V83, P89