Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 131, Issue 10, Pages 636-640Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2010.08.009
Keywords
Long lived individuals; Ataxia telangiectasia mutated; Single nucleotide polymorphism; AP 2 alpha
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Funding
- Science and Technology Bureau of Sichuan Province [2006Z090064]
- West China Hospital Sichuan University [XK05001]
- National Basic Research Program of China [2007CB947802]
- Nature Science Foundation of China [30771228, 30771227]
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Although the ataxia telangiectasia mutated (ATM) gene plays an important role in physiological processes such as sensing DNA damage reducing oxidative stress and protecting telomeres length little information about ATM and longevity is available Therefore we aim to examine the association between genetic variants in promoter of ATM and longevity in Chinese Nonagenarians/Centenarians Genotyping was performed in 789 long-lived individuals (LLIs) and 886 ethnically matched control subjects A single nucleotide polymorphism (SNP rs189037) in the promoter region of ATM gene was identified and significant association between CT genotype and longevity was observed Meanwhile the SNP was able to affect expression of ATM mRNA by differentially binding to AP-2 alpha The CC genotype strongly bound to AP-2 alpha and the IT genotype showed less binding affinity to AP-2 alpha The AP-2 alpha strongly repressed the reporter expression in the CC genotype and showed less repression of the TT genotype driving expression in vitro assay Accordingly TT genotype individuals had highest ATM mRNA expression CT genotype individuals had moderate ATM mRNA expression and the CC genotype individuals had the lowest ATM mRNA. (C) 2010 Elsevier Ireland Ltd All rights reserved
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