Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals

被引：9
作者：
Flachsbart, Friederike [1 ,2 ]
Caliebe, Amke [2 ,3 ]
Nothnagel, Michael [2 ,3 ]
Kleindorp, Rabea [1 ,2 ]
Nikolaus, Susanna [2 ,4 ,5 ]
Schreiber, Stefan [1 ,2 ,5 ]
Nebel, Almut [1 ,2 ]
机构：
[1] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany
[2] Univ Hosp Schleswig Holstein, Kiel, Germany
[3] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany
[4] Univ Kiel, Popgen Biobank, D-24105 Kiel, Germany
[5] Univ Kiel, Dept Gen Internal Med, D-24105 Kiel, Germany
来源：
EUROPEAN JOURNAL OF HUMAN GENETICS | 2010年 / 18卷 / 01期
关键词：
A2M; alpha2-macroglobulin; centenarians; longevity; Alzheimer's disease; age-related diseases; ARGYROPHILIC GRAIN DISEASE; GENETIC ASSOCIATION; HUMAN LONGEVITY; ALPHA-2-MACROGLOBULIN GENE; CENTENARIANS; POLYMORPHISMS; TESTS;
D O I：
10.1038/ejhg.2009.136
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Risk alleles for age-related diseases are expected to decrease in frequency in the population strata of increasing age. Consistent with this hypothesis, earlier studies showed a depletion of the Alzheimer's disease risk factor APOE*epsilon 4 in long-lived individuals (LLIs). To evaluate whether this observation also holds for a previously suggested Alzheimer's disease risk haplotype in the A2M gene, we analyzed this particular haplotype in 1042 German LLIs (aged 95-100 years) and 1040 younger individuals (aged 60-75 years). Our results show a significant depletion of this haplotype in LLIs, thus confirming it as a mortality factor in the elderly. Consequently, our data support an involvement of the suggested A2M risk haplotype in the pathogenesis of Alzheimer's disease and adds new evidence to the risk-allele depletion hypothesis. European Journal of Human Genetics (2010) 18, 59-61; doi:10.1038/ejhg.2009.136; published online 29 July 2009
引用
收藏
页码：59 / 61
页数：3
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