The ECTIM Study

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, e2, e3, and e4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n=722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P=.O4), with a higher frequency of the e4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n=640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the e2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E: B. However, the effect of the e2 allele on triglycerA polipoprotein E (apoE) is a structural component / \ of triglyceride-rich lipoproteins, chylomicrons . X A and very-low-density lipoproteins (VLDLs), and high-density lipoproteins (HDLs). The structural gene locus of this apolipoprotein is polymorphic. Three common alleles designated e2, e3, and e4 code at a single locus from three isoforms, E2, E3, and E4. These three isoforms lead to six apoE phenotypes in plasma Received August 13, 1993; revision accepted June 1, 1994. From SERLIA and INSERM U325 (G.L., J.-M.B., J.-C.F.) and MONICA Lille (G.L., P.A.), Pasteur Institute of Lille (France); MONICA Strasbourg, Laboratoire d'Epidemiologie et de Sante Publique (D.A., P.S.) (France); Belfast MONICA, Department of Epidemiology and Public Health, The Queen University of Belfast (A.E.) (Northern Ireland); MONICA Toulouse, INSERM 326, ORSMIP (J.-P.C, J.-B.R.) (France); and INSERM U258 (A.B., F.C., P.D.) and INSERM SC7 (F.C.), Paris, France. Correspondence to Gerald Luc, SERLIA and INSERM U325, Pasteur Institute of Lille, 1 rue du Professeur Calmette, 59019 Lille Cedex, France. © 1994 American Heart Association, Inc. ide, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations. The magnitude of these effects was large and statistically significant in Lille and Strasbourg, whereas only apoE was increased in Toulouse, and no effect of the e2 allele appeared in Belfast. The e4 allele was associated with increased triglyceride, VLDL-C, apoB, and Lp C-III:B levels and a decreased LpA-I level, but apoC-III, apoE, and Lp E: B levels were similar to those with the apoE3/3 phenotype. The relative risk of myocardial infarction associated with apoE phenotypes compared with E3/3 was found to increase in the following order: E2/2<E3/2<E3/3 (relative risk=l) <E4/ 3=E4/2<E4/4 (P<.05). The presence of e2 and e4 alleles carried a relative risk of 0.73 (P=.O5) and 1.33 (P=.O2), respectively, in a codominant logistic model, and no heterogeneity between centers was demonstrated. In conclusion, men carrying the e4 allele present an atherogenic lipid and lipoprotein profile compared with E3/3 and are at higher risk of coronary heart disease in the populations under study. Men carrying the e2 allele have lower apoB levels and appear to be at lower risk despite higher triglyceride and Lp E:B levels, at least in some regions. This suggests that other genes or environmental factors play an interactive role with the e2 allele on lipid metabolism. ApoE polymorphism, however, seems to explain a modest proportion, 12%, of myocardial infarction cases at the population level. (Arterioscler Thromb. 1994;14:1412-1419.)