Abstract
Apolipoprotein E (APOE) 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer’s disease, but its independent role in cognitive function is unclear. APOE genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Cognitive phenotype and APOE genotype data were used to determine whether APOE variation was significantly associated with cognitive function in this population. Observed allele frequencies for 1776 participants from the HAALSI study [age 40–80years (mean=56.19); 58.2% female] were 58.1% (𝜀3), 25.4% (𝜀4) and 16.5% (𝜀2). Allele distributions were similar to the African super population, but different from all non-African super populations from the 1,000 Genomes Project. The 𝜀3 homozygous genotype was most common (34.9%) and used as the base genotype for comparison in regression models. Four models were tested for each of the five cognitive phenotypes to explore association of APOE variation with cognitive function. In the first model assessing association with all genotypes for all individuals, marginally significant associations were observed for 𝜀2 homozygotes where executive function scored higher by ~0.5 standard deviations (p=0.037, SE=0.23), and for 𝜀3/𝜀4 heterozygotes where visuospatial ability scores were lower (p=0.046, SE=0.14). These did not survive correction for multiple testing. Regional African population differences were observed at the APOE locus. Marginally, significant associations between APOE genotype, and executive function and visuospatial ability indicate the need for larger studies to better examine these associations in African populations. Furthermore, longitudinal data could shed light on APOE genetic association with rate of change, or decline, in cognitive function.
Highlights
Studies conducted in different populations have reported associations between apolipoprotein E (APOE) ε4 and various detrimental outcomes
Significant associations were observed in Model 1 (Table 4) for Apolipoprotein E (APOE) genotypes, where ε2/ε2 was associated with higher levels of executive function by approximately half a standard deviation (β = 0.489, standard error (SE) = 0.57, p = 0.037) and lower levels when participants were heterozygous ε2-carriers, and ε3/ε4 was associated with lower levels of visuospatial cognition (β = −0.286, SE = 0.14, p = 0.046). These effects (f2 = 0.395 and f2 = 0.597, respectively) were not significant after Bonferroni correction for multiple testing (p = 0.337 and 0.416, respectively). This cross-sectional study assessed the potential effect of APOE genetic variation on five measures of cognition in a ruraldwelling South Africa (SA) population
We aimed to address the lack of African data for large cohorts that can be used to examine the genetics of cognition and cognitive decline, in rural areas where vulnerability to cognitive impairment and dementia is becoming a major public health concern (Kobayashi et al, 2019)
Summary
Studies conducted in different populations (mostly of European ancestry) have reported associations between apolipoprotein E (APOE) ε4 and various detrimental outcomes These include susceptibility to, and severity of cardiovascular diseases, HIV infection and its associated comorbidities, late onset Alzheimer’s disease, and recently COVID-19 (Hendrie et al, 1995; Savitz et al, 2006; Burt et al, 2008; Chang et al, 2011; Panos et al, 2013; Kotze et al, 2015; O’Donoghue et al, 2018; Kuo et al, 2020).
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