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Human Molecular Genetics, 2000, Vol. 9, No. 1 57-61
© 2000 Oxford University Press

Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations—the ECTIM Study

Jean-Charles Lambert1, Thierry Brousseau1,3, Véronique Defosse1, Alun Evans4, Dominique Arveiler5, Jean-Bernard Ruidavets6, Bernadette Haas5, Jean-Pierre Cambou6, Gérald Luc2, Pierre Ducimetière7, François Cambien8, Marie-Christine Chartier-Harlin1 and Philippe Amouyel1,+

1INSERM U508 and 2INSERM U325, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille cedex, France, 3Faculté des Sciences Pharmaceutiques et Biologiques, 3 rue du Professeur Laguesse, 59006 Lille cedex, France, 4Belfast MONICA Project, Department of Epidemiology and Public Health, The Queen’s University of Belfast, Belfast BT12 6BJ, UK, 5Strasbourg MONICA Project, Laboratoire d’Epidémiologie, Faculté de Médecine, 67085 Strasbourg cedex, France, 6INSERM U518, Faculté de Médecine Toulouse-Purpan, 31073 Toulouse cedex, France, 7INSERM U258, Hôpital Paul Brousse, 16 avenue Paul Vaillant-Couturier, 94807 Villejuif cedex, France and 8INSERM SC7, 17 rue du Fer à Moulin, 75005 Paris, France

Apolipoprotein E (APOE) is a major protein in lipid metabolism existing in three common isoforms: APOE2, -3 and -4. The {varepsilon}4 allele of the APOE gene (APOE) coding for the APOE4 isoform is associated with an increased risk of myocardial infarction (MI) and of Alzheimer’s disease (AD). Recently, several polymorphisms in the APOE regulatory region have been reported. Some of these have been associated with AD and modified APOE allelic mRNA expression in AD brains. Here, we have investigated whether three of these promoter polymorphisms (–491AT, –427CT and –219GT) can also modify cardiovascular risk. The hypothesis was tested in a large multicentre case–control study of MI, the ECTIM Study, on 567 cases and 678 controls. Among the three APOE promoter polymorphisms tested, only the –219T allele was associated with a significantly increased risk of MI (OR = 1.29, 95% CI: 1.09–1.52, P < 0.003) and the effect was shown to be independent of the presence of the other mutations, including the APOE {varepsilon}2/{varepsilon}3/{varepsilon}4 polymorphism. Moreover, the –219T allele greatly decreased the APOE plasma concentrations in a dose-dependent manner (P < 0.008). These data indicate that the –219GT polymorphism of the APOE regulatory region emerges as a new genetic susceptibility risk factor for MI and constitutes another common risk factor for both neurodegenerative and cardiovascular diseases.

+ To whom correspondence should be addressed. Tel: +33 3 20 87 77 10; Fax: +33 3 20 87 78 94; Email: philippe.amouyel@pasteur-lille.fr


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