Apolipoprotein E Polymorphisms Predict Low Density Lipoprotein Cholesterol Levels and Carotid Artery Wall Thickness but Not Incident Coronary Heart Disease in 12,491 ARIC Study Participants

Abstract

Elevated levels of low density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease, and recent advancements have provided evidence that carotid artery intima-media thickness (IMT) is associated with increased occurrence of cardiovascular events. Apolipoprotein E (ApoE) has been widely studied in regard to its role in lipid transport and metabolism, but the role that ApoE genetic variation plays in relation to carotid artery IMT and risk of incident coronary heart disease remains a subject of debate. In 1987-2001, the authors examined the effect of each ApoE allele (epsilon2, epsilon3, epsilon4) on LDL cholesterol and carotid IMT, as well as the association with coronary heart disease risk, in 12,491 participants of the US Atherosclerosis Risk in Communities Study. ApoE epsilon2, epsilon3, and epsilon4 allele frequencies were determined, respectively, in Whites (0.08, 0.77, 0.15) and African Americans (0.11, 0.67, 0.22). These alleles did not predict incident coronary heart disease in either racial group. The ApoE epsilon2 allele was associated with lower LDL cholesterol and the epsilon4 allele with higher LDL cholesterol in both Whites and African Americans. The ApoE epsilon2 and epsilon4 alleles were associated with carotid IMT measures in both racial groups, but, after adjusting for lipid parameters, only the epsilon4 allele was associated with carotid IMT measures in African Americans.

Effect of APOE polymorphism on obesity and lipid profile in women of differing reproductive status

“…Their study was based on women in the 26 to 63 year age group, and they reported that the E*3/2 genotype was associated with a significantly higher average WHR value compared to E*3/3 and E*3/4 genotypes. The study "Atherosclerosis Risk in Communities" (ARIC) revealed that apoE isoforms are associated with increased BMI in the following order: APOE*2>APOE*3>APOE*4 [26]. That finding was not consistent with our results, where an effect of menopausal group and APOE group on BMI was not detected.…”

Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí Health Aging Study (BHAS)

“…Higher triglyceride levels were found in ε2 carriers. This association was reported in some (6,8), but not all previous investigations (7). The association of the ApoE alleles with plasma lipid levels is a direct consequence of the role of ApoE protein in lipid metabolism.…”

“…The ApoE gene is located on chromosome 19 (4,5) with three common alleles, termed ε2, ε3 and ε4. The ε4 allele has consistently been linked to increases in LDL cholesterol levels (6,7). The ε2 allele has been reported to be linked with higher triglyceride levels in some (6,8), but not all studies (7).…”

Dyslipidemia: Genetics and Role in the Metabolic Syndrome

“…Mutations in APOE are well known to modify LDL-C levels; however, their independent influence on HDL-C levels remains controversial (Sviridov and Nestel, 2007). Nevertheless, associations between APOE SNPs and HDL-C levels in large scale studies have been fairly consistent (Costanza et al, 2005;Frikke-Schmidt et al, 2000;Gronroos et al, 2008;Kataoka et al, 1996;Srinivasan et al, 1999;Volcik et al, 2006;Wilson et al, 1994;Wu et al, 2007).…”