Associations of apolipoprotein E polymorphism with low-density lipoprotein size and subfraction profiles in Arab patients with coronary heart disease Abayomi O. Akanji a, 4 , Cheriyil G. Suresh b , Hasmukh R. Fatania c , Reem Al-Radwan d , Muhammad Zubaid e a Department of Pathology, Kuwait University Faculty of Medicine, Kuwait b Cardiology Unit, Department of Medicine, Mubarak Al-Kabeer Hospital, Kuwait c Department of Biochemistry, Kuwait University Faculty of Medicine, Kuwait d Central Blood Bank, Kuwait e Department of Medicine, Kuwait University Faculty of Medicine, Kuwait Received 24 April 2006; accepted 10 November 2006 Abstract The APOE gene locus has 3 major alleles, E3, E4 and E2, which variably influence coronary heart disease (CHD) risk. Plasma low-density lipoprotein (LDL) profile, another major CHD risk factor, is characterized on the basis of size and density into 2 main patterns: large buoyant LDL and small dense LDL. The latter has also been linked with increased CHD risk. This study investigates associations of specific APOE allelic patterns with LDL size and subfraction profiles in patients with CHD and healthy control subjects. We recruited 2 groups of male subjects: (A) 65 apparently healthy control subjects, median age, 39.0 years (range, 25.0-60.0 years); (B) 50 patients with CHD, median age, 54.0 years (range, 40.0-76.0 years). APOE genotypes were determined by validated polymerase chain reaction-restriction fragment length polymorphism methods, and LDL size and subfractions were assessed by a high-resolution, nongradient polyacrylamide gel electrophoresis technique (LIPOPRINT, Quantimetrix, Redondo Beach, CA). Lipid and other biochemical analyses were done by autoanalyzer techniques. The associations of specific APOE alleles and genotypes with LDL size and subfraction patterns were then assessed. As expected, patients with CHD had a worse atherogenic lipoprotein profile (waist-hip ratio, LDL, uric acid, and apolipoprotein B) than the controls. APOE genotype and allele frequencies were similar for both groups. In either group, median percent large buoyant LDL (pattern A) was greater in controls (51.0% vs 46.5%, P b .001) and percent small dense LDL (pattern B) was greater with CHD (9.0% vs 3.0%, P b .001). The latter also had smaller median particle size (26.5 vs 26.9 nm, P b .001). In controls, percent LDL pattern B was significantly lower with APOE2 than with APO non- E2 (4.0% vs 0.0%, P b .05); in patients with CHD, E2 patients had smaller particle size, and pattern B was significantly lower with non-E2 than with E2 (15.0 vs 8.0, P b .05). With respect to E4, control non-E4 had a smaller median percent LDL pattern B than E4; otherwise, there were no significant findings in relation to APOE type and LDL size and subfractions in both subject groups. These results confirm observations in other populations of increased levels of small dense LDL in patients with CHD. Although the APOE allelic pattern, especially APOE2, could be related to LDL subfraction profiles in control subjects, such associations could not be demonstrated in those with CHD. D 2007 Elsevier Inc. All rights reserved. 1. Introduction Low-density lipoprotein (LDL) particle size is an important determinant of coronary heart disease (CHD) risk; several cross-sectional and prospective studies in white [1-3] and other populations [4] have shown that individuals with predominantly small dense LDL particles (subclass pattern B) are at increased risk for CHD even when levels of LDL cholesterol (LDL-C) are not elevated. Many genetic and environmental factors underlie LDL heterogeneity. These are population dependent [2-5]. Apolipoprotein E (APOE), which plays a major role in endogenous lipoprotein metabolism and tissue distribution, is polymorphic, with 3 common isoforms (E2, E3, and E4) and 6 genotypes (E2E2, E2E3, E3E3, E2E4, E3E4, and E4E4) [6-9]. This allelic pattern is believed to influence risk of many disorders—E4 and CHD [9,10] or Alzheimer 0026-0495/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2006.11.006 4 Corresponding author. Tel.: + 965 531 9476; fax: + 965 533 8905. E-mail address: abayomi@hsc.edu.kw (A.O. Akanji). Metabolism Clinical and Experimental 56 (2007) 484 – 490 www.elsevier.com/locate/metabol