Association of Apo E Polymorphism With Plasma Lipid Levels in a Multiethnic Elderly Population

Abstract

Apolipoprotein E polymorphisms are important determinants of blood lipid levels and have been associated with longevity and atherosclerosis. However, information is limited on the effects of apo E variation on the lipids of nonwhite and elderly individuals. We tested the hypothesis that apo E polymorphisms are associated with plasma lipid levels in an elderly, multiethnic population. Cross-sectional data from 1068 noninstitutionalized individuals from northern Manhattan over the age of 64 who were not on a lipid-lowering diet or drug were analyzed. The ethnic distribution was 34% African-Americans, 47% Hispanics, and 19% non-Hispanic Caucasians. In the entire group, the most prevalent apo E allele was epsilon 3 (76%), followed by epsilon 4 (16%) and epsilon 2 (8%); epsilon 4 was more prevalent in African-Americans (21%) than in non-Hispanic Caucasians (12%) or Hispanics (14%). The apo epsilon 2 allele was the most important correlate of plasma lipids, but association varied across ethnoracial groups. After being adjusted for age, sex, obesity, diabetes mellitus, and alcohol intake, LDL cholesterol levels declined with each apo epsilon 2 allele by 8.8 mg/dL in Hispanics and by 25.6 and 18.1 mg/dL in non-Hispanic Caucasians and African-Americans, respectively (P < .001). No significant independent effect was noted for any apo E genotype on HDL cholesterol. Overall, there was a reduction in the total/HDL cholesterol ratio, per apo epsilon 2 allele, of 0.82 in non-Hispanic Caucasians and 0.43 and 0.48 in African-American and Hispanic individuals, respectively (P < .05). In a multivariate model, apo epsilon 4 did not significantly affect plasma lipid levels. Plasma triglyceride levels were inversely correlated with the number of apo epsilon 4 alleles (175, 159, and 143 mg/dL with 0, 1, and 2 alleles, respectively; P =.002), and this effect increased with age. Thus, in an elderly, multiethnic population, apolipoprotein E polymorphisms were important determinants of blood lipids, with differing effects depending on ethnicity. The presence of apo epsilon 2 was associated with lower LDL cholesterol levels and total/HDL cholesterol ratio, although apo epsilon genotype did not influence HDL cholesterol levels. Prospective studies are needed to test whether apo epsilon 2 protects against incident cardiovascular disease in the elderly.

Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

“…However, the amplitude of the effect may be modulated by ethnic background and environmental factors (7,32). In the present study, associations of APOE genotypes with serum lipids were consistent with the well-identified effects of APOE (33)(34)(35).…”

“…The most plausible reasons for these inconsistencies are differences in statistical treatment, different sampling schemes or differ-ent environmental factors. It is likely that the influence of the APOE gene on serum lipid levels may be modified by other genetic or environmental factors among different populations (7,32).…”

Multiple genetic determinants of plasma lipid levels in Caribbean Hispanics

“…Approximately half of the variability in plasma lipid levels is determined by genetic factors [1]. Several genes, such as the apolipoprotein A5 (APOA5), apolipoprotein B (APOB), apolipoprotein E (APOE), and cholesterol ester transfer protein (CETP) genes, have been reported to be related to the lipid profiles in whites and blacks [2][3][4][5]. However, only few of them (APOA5, APOE, and CETP) have been investigated in Hispanics [6][7][8].…”

“…Certain population-specific genes may alter disease susceptibility of Hispanics by influencing lipid profiles or changing host response to detrimental lipid profiles. For example, the ε4 allele of APOE is associated with an increase of low density lipoprotein cholesterol (LDL-C) levels by 2.6 mg/dL in Caucasian men but 8.5 mg/dL in Hispanic men [4,12]. Furthermore, an elevated LDL-C level leads to a more prominent progression in carotid atherosclerosis in Hispanics than other ethnic groups [13], suggesting that race-ethnicity may influence the relationship between genes, lipids and CVD risk.…”

Apolipoprotein E and cardiovascular diseases

“…In elderly subjects, as well as in children, there is less difference in LDL cholesterol levels in individuals carrying the ε4 allele versus non-ε4 carriers. [4,5] Recently, the role of apoE has been extended also to intracellular lipoprotein traffi cking, but there is limited information on whether these are infl uenced by genotype variations. [6,7] As mentioned above, many studies have investigated the association of apoE genotype with CVD.…”