Apolipoprotein E epsilon 4 and incidence of Alzheimer disease in a community population of older persons

Apolipoprotein E epsilon 4 and incidence of Alzheimer disease in a community population of older persons
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DOI:
10.1001/jama.277.10.822
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发表时间:
1997-03-12
影响因子:
120.7
通讯作者:
Mayeux, R
Mayeux, R
中科院分区:
医学1区
文献类型:
--
作者:
Evans, DA;Beckett, LA;Mayeux, R

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客观。-在特定人群中检测载脂蛋白E状态与阿尔茨海默病(AD)风险之间的关系,并估计归因于β 4等位基因的AD事件分数。基于社区的队列研究。设置。-东波士顿,马萨诸塞州。随机抽取578名年龄在65岁及以上的社区居民,他们没有AD。通过统一的结构化评估进行AD的临床诊断。AD风险增加与等位基因的存在是小于在大多数家庭和病例对照研究中发现的。与携带H13/H14基因型的人相比,携带H14/H14或H13/H14基因型的人发生疾病的风险是携带H13/H13基因型的人的2.27倍(95%置信区间,1.06-4.89)。AD的发病率中,E14等位基因只占很小一部分;如果该等位基因不存在或对疾病风险没有影响,发病率仅会降低13.7%。AD的风险的影响,等位基因没有出现随年龄而变化。载脂蛋白E β 4等位基因是AD的重要遗传危险因素,但在这项基于人群的研究中占疾病发生的相当小的比例。有必要继续努力确定其他环境和遗传风险因素。
Objective.-To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon 4 allele.Design.-Community-based cohort study.Setting.-East Boston, Mass.Participants.-A random sample of 578 community residents aged 65 years and older free of AD.Main Outcome Measure.-Clinical diagnosis of AD by uniform, structured evaluation.Results.-The increased risk of AD associated with the presence of the epsilon 4 allele was less than that found in most family and case-control studies. Persons with the epsilon 4/epsilon 4 or epsilon 3/epsilon 4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon 3/epsilon 3 genotype. The epsilon 4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon 4 allele on risk of AD did not appear to vary with age.Conclusions.-The apolipoprotein E epsilon 4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.