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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:775.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

In-Depth Haplotype Analysis of ABCA1 Gene Polymorphisms in Relation to Plasma ApoA1 Levels and Myocardial Infarction

David-Alexandre Tregouet; Sylvain Ricard; Viviane Nicaud; Isabelle Arnould; Stéphane Soubigou; Marie Rosier; Nicolas Duverger; Odette Poirier; Sandrine Macé; Frank Kee; Caroline Morrison; Patrice Denèfle; Laurence Tiret; Alun Evans; Jean-Francois Deleuze; Francois Cambien

From INSERM U525 (D.-A.T., V.N., O.P., L.T., F.C.), Paris, France; Functional Genomic (S.R., I.A., S.S., M.R., N.D., S.M., P.D., J.-F.D.), Aventis-SA, Evry and Vitry s/Seine, France; Queen’s University Belfast (F.K., A.E.), Northern Ireland, United Kingdom; and the Monica Project (C.M.), Glasgow Royal Infirmary, Scotland, United Kingdom.

Correspondence to D. A. Tregouet, INSERM U525, Faculté de Médecine de la Pitié-Salpétrière, 91 boulevard de l’Hopital, 75364 Paris, France. E-mail david.tregouet{at}chups.jussieu.fr

Objective— By regulating the cellular cholesterol efflux from peripheral cells to high-density lipoprotein, the ABCA1 protein is suspected to play a key role in lipid homeostasis and atherosclerosis. Twenty-six polymorphisms of the ABCA1 gene were genotyped and tested for association with plasma levels of ApoA1 and myocardial infarction (MI) in the ECTIM study.

Methods and Results— In addition to single-locus analysis, a systematic exploration of all possible haplotype effects was performed, with this exploration being performed on a minimal set of "tag" polymorphisms that define the haplotype structure of the gene. Two polymorphisms were associated with plasma levels of ApoA1, 1 in the promoter (C-564T) and 1 in the coding (R1587K) regions, whereas only 1 polymorphism (R219K) was associated with the risk of MI. However, no haplotype effect was detected on ApoA1 variability or on the risk of MI.

Conclusion— ABCA1 gene polymorphisms but not haplotypes are involved in the variability of plasma ApoA1 and the susceptibility to coronary artery disease.

Key Words: ABC transporters • haplotypes • atherosclerosis • coronary artery disease

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