摘要
有家族史的阿尔茨海默病(AD)可能增加与载脂蛋白E基因的等位基因ε-4表型表达相关的累积风险。在本研究中,我们比较了慢性疾病筛查项目中537例南非人载脂蛋白Eε-2(rs7412)和ε4(rs429358)的基因型分布及等位基因频率,以此确定阿尔茨海默病家族史是否调节了血脂代谢功能的表达。研究发现载脂蛋白Eε-2和ε4的基因型分布APOEε-2基因型分布在有家族史(n = 67)和没有家族史(n = 470)的阿尔茨海默病患者中有显著差别(p = 0.034)。低密度脂蛋白胆固醇水平与阳性家族史阿尔茨海默病患者身体活动呈负相关(p < 0.001),而与阴性家族史阿尔茨海默病患者身体活动关系不显著 (p = 0.257)。类似于当前在诊断家族性高胆固醇血症等单基因血脂异常中的应用,人们认为关于家族史的临床调查是在慢性疾病风险管理中适合的载脂蛋白E基因表型的决定因素。据我们所知,这是第一次研究证明阿尔茨海默病家族史在血脂异常表型表达中的调节作用与载脂蛋白Eε-4等位基因有关。我们的发现为新的临床应用载脂蛋白E基因型作为识别用于降低心血管疾病、预防阿尔茨海默病累积风险为目的的最大益处在于干预早期生活方式为基础的血脂异常患者基因群的新手段提供了科学论据支持。
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
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. 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.
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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
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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