Influence of cholesteryl ester transfer protein, peroxisome proliferator-activated receptor alpha, apolipoprotein E, and apolipoprotein A-I polymorphisms on high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations: the Prospective Epidemiological Study of Myocardial Infarction study.
The plasma level of high-density lipoprotein cholesterol (HDL-C) is known to be inversely associated with cardiovascular risk. However, besides lifestyle, gene polymorphism may influence the HDL-C concentration. The aim of this study was to investigate the possibility of interactions between CETP, PPARA, APOE, and APOAI polymorphisms and HDL-C, apolipoprotein (apo) A-I, lipoprotein (Lp) A-I, and Lp A-I:A-II in a sample selected from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study population who remained free of cardiovascular events over 5 years of follow-up. Healthy individuals (857) were randomly selected for genotyping the PRIME study subjects. The population was selected so as to provide 25% of subjects in the lowest tertile of HDL-C (< or = 28 mg/dL) in the whole PRIME study sample, 25% of subjects in the highest tertile of HDL-C (> or = 73 mg/dL), and 50% of subjects in the medium tertile of HDL-C (28-73 mg/dL). Genotyping was performed by using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assay. The CETP A373P rare allele c was less frequent in the group of subjects with high HDL-C, apo A-I, Lp A-I, and Lp A-I:A-II concentrations. Apolipoprotein A-I and Lp A-I were also found to be higher in the presence of the epsilon2 allele coding for APOE. The effect of the CETP A373P rare allele c on HDL-C was independent of all tested parameters except triglycerides. The respective effect of these polymorphisms and triglycerides on cardiovascular risk should be evaluated prospectively.
Do
Hong Quang
HQ
Faculté de Pharmacie, Université de Nantes, Laboratoire de Biochimie, EA3823, 1 rue Gaston Veil, 44035 Nantes, France.
Nazih
Hassan
H
Luc
Gérald
G
Arveiler
Dominique
D
Ferrières
Jean
J
Evans
Alun
A
Amouyel
Philippe
P
Cambien
François
F
Ducimetière
Pierre
P
Bard
Jean-Marie
JM
D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D016633:Apolipoprotein A-II / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D005602:France; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D009660:Northern Ireland; D047493:PPAR alpha / Q000235:genetics*; D011110:Polymorphism, Genetic
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D047493:PPAR alpha; D004247:DNA