Authors: Chen T; Dong B; Lu Z; Tian B; Zhang J; Zhou J; Wu H; Zhang Y; Wu J; Lin P; Zhang J; Xu H; Mo X
Abstract: 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-2alpha. The CC genotype strongly bound to AP-2alpha, and the TT genotype showed less binding affinity to AP-2alpha. The AP-2alpha 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.
Keywords: Aged, 80 and over; Asian Continental Ancestry Group; Cell Cycle Proteins/*biosynthesis/*genetics; China; DNA-Binding Proteins/*biosynthesis/*genetics; Female; Gene Expression Regulation/*physiology; Genotype; Humans; Longevity/*physiology; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic/*physiology; Protein-Serine-Threonine Kinases/*biosynthesis/*genetics; Transcription Factor AP-2/genetics/metabolism; Tumor Suppressor Proteins/*biosynthesis/*genetics|
Journal: Mechanisms of ageing and development Volume: 131 Issue: 10 Pages: 636-40 Date: Sept. 8, 2010 PMID: 20816691 |
Chen T, Dong B, Lu Z, Tian B, Zhang J, Zhou J, Wu H, Zhang Y, Wu J, Lin P, Zhang J, Xu H, Mo X (2010) A functional single nucleotide polymorphism in promoter of ATM is associated with longevity. Mechanisms of ageing and development 131: 636-40.
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