Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol152.Issue2.Oct2000:

Atherosclerosis 152 2000 475 – 488 Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project F. Schiele a , D. De Bacquer b , M. Vincent-Viry a , U. Beisiegel c , C. Ehnholm d , A. Evans e , A. Kafatos f , M.C. Martins g , S. Sans h , C. Sass a , S. Visvikis a,i , G. De Backer b , G. Siest a,i, , The ApoEurope group a Laboratoire du Centre de Me´decine Pre´6enti6e, 2 , a6enue du Doyen Jacques Parisot, 54500 , Vandoeu6re-le`s-Nancy, France b Department of Public Health, Uni6ersity of Gent, Gent, Belgium c Medizinische Klinik, Uni6ersita¨ts-Krankenhaus Eppendorf, Hamburg, Deutschland d National Public Health Institute, Department of Biochemistry, Helsinki, Finland e Department of Epidemiology and Public Health, the Queen ’ s Uni6ersity of Belfast, Belfast, UK f Uni6ersity of Crete, Faculty of Medicine, Heraklion, Crete, Greece g Unidade de Quimica Clinica, Instituto Nacional de Saude, Lisbon, Portugal h Programa Cronicat, Institute of Health Studies, Barcelona, Spain i Uni6ersite´ Henri Poincare´ Nancy I Inserm U- 525 , 54000 , Nancy, France Received 5 April 1999; received in revised form 20 October 1999; accepted 13 December 1999 Abstract As part of the ApoEurope Project, the apolipoprotein E apo E serum concentration and polymorphism were determined in 6934 healthy subjects aged 25 – 64 years recruited in six European countries: Finland; France; Greece; Northern Ireland; Portugal and Spain. Age and sex influenced apo E concentration with concentrations being significantly higher in men than in women for those aged between 25 and 44 years. The age effect differed between the sexes after the age of 44 years, displaying a linear increase in women and a plateau in men. As expected, the serum apo E concentration was highest in o2 carriers and lowest in o4 carriers in each country with a significantly higher frequency of the o4 allele in the northern regions. The main finding of this study was a clear increasing North – South gradient in serum apo E concentration independent of age, sex and apo E genotype. In subjects aged B 45 years and with the o3o3 genotype, apo E concentration was higher in the South-East Greece as compared to the North by 20 for men and 32 for women. In addition to the genetic polymorphism, the geographical area is an important factor to take into account when studying serum apo E concentration in multicentre studies and defining reference values. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Apolipoprotein E polymorphism; Apolipoprotein E concentration; Multicentre study; Epidemiology; Cardiovascular risk www.elsevier.comlocateatherosclerosis

1. Introduction

Apolipoprotein apo E is an important component of plasma lipoproteins and influences lipoprotein metabolism through its action as a receptor ligand. Other important roles of apo E include immunomodu- lation and nerve regeneration. Apo E is polymorphic with three common alleles: o2, o3 and o4 [1]. More recently polymorphisms in the promoter region have been described [2,3]. The serum apo E concentration and cholesterol concentration are in part determined by the common apo E polymorphism; thus the o2 allele is associated with lower serum cholesterol and higher apo E concentration, whereas the o4 allele is associated with a high serum cholesterol and low apo E concentration [4]. A number of studies [5,6] have demonstrated that the o4 allele is associated with an increased risk of coronary artery disease CAD. It is unclear whether this effect is mediated through the effect of the apo E genotype on lipids or through other mechanisms [7]. Furthermore, the different rates of CAD observed in European countries may partly been explained by the Corresponding author. Tel.: + 33-3-83-448720; fax: + 33-3-83- 448721. E-mail address : gerard.siestcmp.u-nancy.fr G. Siest. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 5 0 1 - 8 prevalence of apo E genotypes. The role of the apo E serum concentration as a risk factor for CAD has not been investigated. During recent years several studies have demon- strated that apo E genotype is a determinant of suscep- tibility to Alzheimer’s disease AD with o 4 homozygotes at increased risk for review see [1]. This finding has provided important clues to the pathogene- sis of AD. The role of the apo E serum concentration as a risk factor for AD has been studied but the results have been controversial [8,9]. A prerequisite for the proper investigation of serum apo E concentrations as a risk marker is an understanding of the factors deter- mining serum apo E concentration in health and the establishment of serum reference values The ApoEurope Project, supported by the European Community, consists of three parts: part I, epidemiol- ogy of apo E concentration; part II, role of apo E in cardiovascular disease; part III, role of apo E in Alzheimer’s disease. The specific objectives of this pa- per part I of ApoEurope are: a, to describe the distribution of the serum apo E concentration across different European populations; b, to study some factors affecting interindividual variation in serum apo E concentration: apo E genotype, age, sex, and geo- graphical area; and c, to provide apo E genotype related values for serum apo E concentration in four European regions. For these purposes, six research units were selected for collaboration.

2. Materials and methods