Apolipoprotein E genotyping and questionnaire-based assessment of lifestyle risk factors in dyslipidemic patients with a family history of Alzheimer’s disease: test development for clinical application
The cholesterol-raising properties of the apolipoprotein E (APOE) epsilon-4 (ε-4) allele has been validated in the South African population. Mounting evidence supports the added value of APOE genotyping for the evaluation of cardiovascular risk in dyslipidemic patients beyond its established role in the diagnosis of late-onset Alzheimer’s disease (AD). The aim of this study was to determine the potential benefits of combining AD family history with questionnaire-based lifestyle assessment to facilitate the clinical interpretation of APOE genotyping results. A total of 580 unrelated South African individuals prospectively enrolled in a chronic disease screening program incorporating a genetic component (2010–2015) was selected for inclusion in this study based on the presence (75) or absence (505) of AD family history. Biochemical assessment of their lipid profiles was performed according to standard laboratory protocols. All study participants were genotyped for the APOE ε-2/ε-3/ε-4 alleles using allele-specific TaqMan real-time polymerase chain reaction technology. In patients without a family history of AD, APOE genotype modified the relationship between alcohol intake and body mass index (p = 0.026), with a significant positive correlation noted between these parameters being limited to ε-4 allele carriers. APOE genotype also modified the association between alcohol intake and total serum cholesterol in patients with a positive family history of AD (p = 0.026). We demonstrated the benefits of a questionnaire-based approach for assessment of lifestyle risk factors to facilitate clinical interpretation of APOE genotyping results for targeted intervention in a genetic subgroup of dyslipidemic patients at increased risk for AD.
KeywordsApolipoprotein E Dyslipidemia Alzheimer’s disease Personalized genomics
This work is based on the research supported in part by the National Research Foundation (NRF) of South Africa (UID 83962). The Grantholder acknowledges that opinions, findings and conclusions or recommendations expressed in any publication generated by the NRF supported research are that of the authors, and that the NRF accepts no liability in this regard. We also gratefully acknowledge the financial support from Winetech in accordance with the implementation of the Wine Industry innovation funding collaboration initiative under the sector innovation fund with the Department of Science and Technology (DST) (number:0370/2014).
Compliance with ethical standards
Prof Kotze is a director and shareholder of Gknowmix (Pty) Ltd. that has developed a database tool for research translation under the auspices of the Innovation Centre of the South African Medical Research Council.
Conflict of interest
The other authors declared no conflict of interest and no writing assistance was obtained in the preparation of this manuscript.
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