Journal
CURRENT ALZHEIMER RESEARCH
Volume 12, Issue 3, Pages 210-217Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205012666150302154354
Keywords
Alzheimer's disease; apolipoprotein E; dyslipidemia; family history; genotype-phenotype association; personalized genomics
Categories
Funding
- National Research Foundation (NRF) of South Africa [UID 83962]
- Winetech
- Technology for Human Resources and Industry Program (THRIP)
- NRF
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Having a family history of Alzheimer's disease (AD) may potentiate cumulative risk associated with phenotypic expression of the epsilon-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE epsilon-2 (rs7412) and epsilon -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE epsilon-2 (p=0.034) as well as APOE epsilon-4 (p=0.038) were found between study participants with (n=67) and without (n=470) a family history of AD. LDL cholesterol levels were inversely associated with physical activity in the study group with a positive family history of AD (p<0.001) but not in those with a negative family history of AD (p=0.257). Similar to its existing use in the diagnosis of monogenic dyslipidemias such as familial hyper-cholesterolemia, clinical inquiry regarding family history was identified as an important determinant of eligibility for APOE genotyping performed in the context of chronic disease risk management. To our knowledge, this is the first study to demonstrate the modulating influence of AD family history on expression of a dyslipidemic phenotype associated with the APOE epsilon-4 allele. Our findings provide the scientific rationale supporting a novel clinical application for APOE genotyping as a means of identifying a genetic subgroup of dyslipidemic patients set to derive the greatest benefit from early lifestyle-based interventions aimed at decreasing cumulative risk for cardiovascular disease and prevention of AD later in life.
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