长寿个体中阿尔茨海默病潜在 A2M 风险单倍型耗竭。
Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals.
机构信息
Institute of Clinical Molecular Biology, Christian-Albrechts University and University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
出版信息
Eur J Hum Genet. 2010 Jan;18(1):59-61. doi: 10.1038/ejhg.2009.136.
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*epsilon4 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.
与年龄相关疾病的风险等位基因预计会在年龄不断增长的人群中减少频率。与这一假说一致，早期的研究表明，在长寿个体（LLIs）中，阿尔茨海默病风险因子 APOE*epsilon4 减少。为了评估这一观察结果是否也适用于 A2M 基因中先前提出的阿尔茨海默病风险单倍型，我们分析了 1042 名德国 LLI（年龄 95-100 岁）和 1040 名较年轻个体（年龄 60-75 岁）的这一单倍型。我们的研究结果表明，在 LLI 中该单倍型显著减少，因此证实其是老年人的死亡因素。因此，我们的数据支持了所提出的 A2M 风险单倍型在阿尔茨海默病发病机制中的作用，并为风险等位基因减少假说提供了新的证据。
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