Comparative study of apolipoprotein-E polymorphism and plasma lipid levels in dyslipidemic and asymptomatic subjects, and their implication in cardio/cerebro-vascular disorders Cla ´ udia N. Ferreira a,b,c , Maria G. Carvalho a , Ana P.S.M. Fernandes a , Luciana M. Lima a , Andre ´ ia A. Loures-Valle d , Julizar Dantas e , Zolta ´ n Janka f , Andra ´ s Palota ´s g, *, Marinez O. Sousa a a Departamento de Ana ´lises Clı´nicas e Toxicolo ´gicas, Faculdade de Farma ´cia, Universidade Federal de Minas Gerais, Avenida Anto ˆnio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil b Prefeitura Municipal de Belo Horizonte, Laborato ´rio Distrital Padre Eusta ´quio, Rua Padre Eusta ´quio 1591, 30720-100 Belo Horizonte, Minas Gerais, Brazil c Fundac ¸a ˜o Hospitalar do Estado de Minas Gerais, Maternidade Odete Valadares, Avenida Contorno 9494, 30110-130 Belo Horizonte, Minas Gerais, Brazil d Departamento de Aterosclerose, Hospital Socor, Avenida Contorno 10500, Barro Preto, 30110-060 Belo Horizonte, Minas Gerais, Brazil e Petrobras - Refinaria Gabriel Passos, Rodovia Ferna˜o Dias, km 427, 32530-000 Betim, Minas Gerais, Brazil f Department of Psychiatry, Albert Szent-Gyo ¨rgyi Clinical Center, Faculty of Medicine, University of Szeged, H-6725 Szeged, Semmelweis u. 6, Hungary g Asklepios-Med Bt. (Private Practice and Research Center), H-6722 Szeged, Kossuth Lajos sgt. 23, Hungary 1. Introduction Dyslipidemia is an important risk factor associated with athero- sclerotic events, including cardio/cerebro-vascular diseases, the main causes of death in industrialized countries (Giuliano et al., 2005; Ineu et al., 2006). A major focus of recent research on these maladies has been to understand the molecular basis of athero- sclerosis and the identification of the role of apolipoprotein-E (apoE) in this process (Greenow et al., 2005). The apoE is a multi- functional protein that plays a key role in the metabolism of cholesterol and triglyceride (Tg) by binding to receptors in the liver and helping to mediate clearance of remnant particles (Mozas et al., 2003; Mendes-Lana et al., 2007). In addition, the role of apoE alleles and isoforms in the etiology and pathogenesis of Alzheimer’s disease (AD) has also been recently discussed by several authors (Al-Khedhairy, 2004; Altamura et al., 2007; Azad et al., 2007; Takei et al., 2009). The human apoE gene is located on chromosome 19q13.2, and encodes a polymorphic protein of 299 amino-acids (Forti et al., 2003; Giassakis et al., 2007; Saidi et al., 2007) which is synthesized in a variety of tissues, including the liver, brain, spleen and kidney (Minihane et al., 2007). The three main apoE isoforms (E2, E3, and Neurochemistry International 56 (2010) 177–182 ARTICLE INFO Article history: Received 10 September 2009 Received in revised form 29 September 2009 Accepted 30 September 2009 Available online 9 October 2009 Keywords: Apolipoprotein-E Cholesterol Dyslipidemia High density lipoprotein (HDL) Lipid profile Low density lipoprotein (LDL) Polymorphism Risk factors ABSTRACT Polymorphisms in the apolipoprotein-E (apoE) gene may modulate lipoprotein metabolism at different steps and influence total and low density lipoprotein (LDL) cholesterol (LDLc) levels, as well as other lipid features. Population studies have documented significant differences in the frequency of apoE alleles which are related to the prevalence of various cardio-vascular and neuro-psychiatric diseases. In this study, the apoE genotypes and allele frequencies were analyzed in 216 individuals (109 dyslipidemic and 107 normo-lipidic subjects), and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein levels, as well as risk factors was evaluated. In normo-lipidic volunteers, the frequencies of e2, e3 and e4 alleles were 0.042, 0.832 and 0.126, while in dyslipidemic subjects 0.046, 0.835 and 0.119, respectively. No significant difference was observed among e2, e3 or e4 and plasma lipid-lipoprotein levels in the dyslipidemic group. In normo-lipidemics, however, total cholesterol, LDLc and non-HDLc plasma levels were significantly lower in e2 subjects when compared to e3 and e4 individuals. The allelic frequencies of apoE e2, e3 and e4 were similar in dyslipidemic and normo-lipemic subjects, suggesting that apoE polymorphisms have no effect on plasma lipid-lipoprotein levels in dyslipidemic subjects. In contrast, in normo-lipemic subjects the e2 allele showed to be associated with lower total cholesterol and LDLc levels, the mark of a better lipid profile. Depending on other co-existing factors, the e2 allele, therefore, may play either a protective or pathogenic role. This elementary knowledge is a fundamental prerequisite for a possible diagnostic application of these lipoproteins as biomarkers to predict adverse cardio-vascular and/or neuro-psychiatric maladies. ß 2009 Elsevier Ltd. All rights reserved. * Corresponding author. Tel.: +36 30 255 6225. E-mail address: palotas@asklepios-med.eu (A. Palota ´ s). Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint 0197-0186/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuint.2009.09.016