Apolipoprotein E and mortality in African-Americans and Yoruba

Abstract

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE ε4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 ( hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations

“…Earlier studies of African Americans using the same data from North Carolina and northern Manhattan (7-9) combined the 3/4 and 4/4 genotypes and did not find an association with the presence of the 4 allele. However, the analysis of the data from Indianapolis did reveal a significant association with the number of 4 alleles among individuals younger than 75 years who were not demented at baseline (10). In a meta-analysis of APOE and AD, Farrer and colleagues (1) also found a significant association in African Americans with 4/4, but not 3/4.…”

“…Two studies of African Americans did not find an association with 4 (7-9). In a third study, the number of 4 alleles was associated with mortality in persons younger than 75 years (10). A study in Korea did not find a significant difference in the allele frequencies between centenarians and younger controls.…”

“…Data for Nigerians older than 65 years in the IndianapolisIbadan Dementia Study suggest little or no relationship between genotype and mortality, but the data are not sufficient to draw firm conclusions (10). The estimated risk for carriers of the 4 allele (3/4 and 4/4 combined) is 1.05 (0.87-1.25), which is the same as the estimate for African Americans (1.05, 0.94-1.17).…”

“…Genotype data are also available for 396 African Americans in Indianapolis in two age groups: younger and older than 75 years. This includes 343 persons without dementia and 41 with dementia (10,14). Genotype frequencies for younger ages from two studies help to anchor the estimates of the allele frequencies (15,16) but do not change the parameter estimates appreciably.…”

Cholesterol, APOE genotype, and Alzheimer disease

“…However, the possession of the APOE-ε4 allele was not associated with mortality risk in this cohort. 44 For this analysis, the clinically assessed normal group was combined with the good performance group in order to use more of the biomarker data in the analysis. It is possible that there may have been undiagnosed cases of mild cognitive impairment or dementia in this group; however, analysis using just the clinically diagnosed normal group for comparison to the AD group revealed similar and significant cholesterol and APOE interaction.…”