载脂蛋白E ε2等位基因对老年男性的健康保护作用及不良影响
Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in older men.
作者信息
Kulminski Alexander M, Ukraintseva Svetlana V, Arbeev Konstantin G, Manton Kenneth G, Oshima Junko, Martin George M, Il'yasova Dora, Yashin Anatoli I
机构信息
Center for Population Health and Aging, Duke University, Trent Hall, Room 002, Trent Drive, Box 90408, Durham, NC 27708, USA.
出版信息
J Am Geriatr Soc. 2008 Mar;56(3):478-83. doi: 10.1111/j.1532-5415.2007.01574.x. Epub 2008 Jan 4.
OBJECTIVES
To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon2-containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (> or = 65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections.
DESIGN
Retrospective cross-sectional study.
SETTING
The unique disability-focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files.
PARTICIPANTS
One thousand seven hundred thirty-three genotyped individuals interviewed regarding IADL disabilities.
MEASUREMENTS
Indicators of IADL impairments, five geriatric disorders, and epsilon2-containing genotypes.
RESULTS
The epsilon2/3 genotype is a major contributor to adverse associations between the epsilon2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53-6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33-0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28-3.72). Adjustment for five diseases does not significantly alter the adverse association between epsilon2-containing genotypes and disability. Protective effects of the epsilon2/3 genotype for CHD (OR=0.52, 95% CI=0.27-0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71-7.14) for men hold in multivariate models with both these factors included. No significant associations between the epsilon2-containing genotypes and IADL are found in women.
CONCLUSION
The epsilon2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that epsilon2-containing genotypes can be unfavorable factors for the health and well-being of aging men.
目的
重新审视常见载脂蛋白E（APOE）基因多态性的健康保护作用，重点关注含APOE ε2基因型与65岁及以上老年男性和女性日常生活工具性活动（IADL）受损之间的联系，并研究已诊断的冠心病（CHD）、阿尔茨海默病、结直肠癌、黄斑变性和动脉粥样硬化如何介导这些联系。
设计
回顾性横断面研究。
背景
来自1999年全国长期护理调查基因子样本的独特的以残疾为重点的数据，与医疗保险服务使用档案相关联。
参与者
1733名接受IADL残疾访谈的基因分型个体。
测量指标
IADL受损指标、五种老年疾病和含ε2基因型。
结果
ε2/3基因型是男性中ε2等位基因与IADL残疾之间不良关联的主要促成因素（优势比（OR）=3.09，95%置信区间（CI）=1.53 - 6.26），尽管它对冠心病有显著保护作用（OR = 0.55，95% CI = 0.33 - 0.92），而冠心病与IADL残疾呈负相关（OR = 2.18，95% CI = 1.28 - 3.72）。对五种疾病进行调整后，含ε2基因型与残疾之间的不良关联没有显著改变。在同时包含这两个因素的多变量模型中，男性中ε2/3基因型对冠心病的保护作用（OR = 0.52，95% CI = 0.27 - 0.99）和对IADL的有害作用（OR = 3.50，95% CI = 1.71 - 7.14）依然存在。在女性中未发现含ε2基因型与IADL之间存在显著关联。
结论
ε2等位基因在男性中可发挥双重作用，保护他们免受某些健康疾病影响，同时也会促进其他疾病发生。与残疾的强烈负相关关系表明，含ε2基因型可能是老年男性健康和福祉的不利因素。
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