基于阿尔茨海默病家族史对载脂蛋白E基因分型的临床相关性研究

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. Kotz

Affiliation:

关键词: 阿尔茨海默病；载脂蛋白E；血脂异常；家族史；遗传相关性研究；个体化的基因组学

摘要: 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.

Cite this article as:

Hilmar K. Luckhoff, Theresa Brand, Dawid P. van Velden, Martin Kidd, Leslie R. Fisher, Susan J. van Rensburg and Maritha J. Kotz , 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