Abstract
Having a family history of Alzheimer’ s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -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 ε-2 (p=0.034) as well as APOE ε-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 hypercholesterolemia, 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 ε-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.
Keywords: Alzheimer’ s disease, apolipoprotein E, dyslipidemia, family history, genotype-phenotype association, personalized genomics.
Current Alzheimer Research
Title:Clinical Relevance of Apolipoprotein E Genotyping Based on a Family History of Alzheimer's Disease
Volume: 12 Issue: 3
Author(s): Hilmar K. Luckhoff, Theresa Brand, Dawid P. van Velden, Martin Kidd, Leslie R. Fisher, Susan J. van Rensburg and Maritha J. Kotze
Affiliation:
Keywords: Alzheimer’ s disease, apolipoprotein E, dyslipidemia, family history, genotype-phenotype association, personalized genomics.
Abstract: Having a family history of Alzheimer’ s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -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 ε-2 (p=0.034) as well as APOE ε-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 hypercholesterolemia, 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 ε-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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Cite this article as:
K. Luckhoff Hilmar, Brand Theresa, P. van Velden Dawid, Kidd Martin, R. Fisher Leslie, J. van Rensburg Susan and J. Kotze Maritha, Clinical Relevance of Apolipoprotein E Genotyping Based on a Family History of Alzheimer's Disease, Current Alzheimer Research 2015; 12 (3) . https://dx.doi.org/10.2174/1567205012666150302154354
DOI https://dx.doi.org/10.2174/1567205012666150302154354 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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