Abstract
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*ɛ4 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.
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Acknowledgements
We thank all study participants for their cooperation. We acknowledge the laboratory personnel of the Institute of Clinical Molecular Biology for excellent technical assistance and the staff of the Popgen Biobank for expert help with the sample recruitment. This study was supported by the DFG excellence cluster ‘Inflammation at Interfaces’ and the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN-2).
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Flachsbart, F., Caliebe, A., Nothnagel, M. et al. Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals. Eur J Hum Genet 18, 59–61 (2010). https://doi.org/10.1038/ejhg.2009.136
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DOI: https://doi.org/10.1038/ejhg.2009.136
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