A functional single nucleotide polymorphism in promoter of ATM is associated with longevity
A functional single nucleotide polymorphism in promoter of ATM is associated with longevity
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ATM 启动子中的功能性单核苷酸多态性与长寿相关。
DOI：
10.1016/j.mad.2010.08.009
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发表时间：
2010-10-01
影响因子：
5.3
通讯作者：
Mo, Xianming
中科院分区：
文献类型：
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作者：
Chen, Tie;Dong, Birong;Mo, Xianming
虽然共济失调毛细血管扩张症突变（ataxia telangiectasia mutated，ATM）基因在感知DNA损伤、减少氧化应激和保护端粒长度等生理过程中发挥重要作用，但关于ATM基因与长寿的相关性研究甚少。因此，我们旨在研究ATM基因启动子区的遗传变异与中国百岁老人长寿的关系。和886名种族匹配的对照组受试者发现ATM基因启动子区的SNP rs 189037与寿命显著相关，同时该SNP可通过与AP-2 α的差异结合影响ATM mRNA的表达，CC基因型与AP-2 α的结合强，AP-2 α和IT基因型对AP-2 α的结合亲和力较低。2 α强烈抑制CC基因型中的报告基因表达，并且在体外测定中显示对TT基因型驱动表达的较少抑制。因此，TT基因型个体具有最高的ATM mRNA表达，CT基因型个体具有最高的ATM mRNA表达。ATMmRNA的表达在CC基因型个体中最低。(C)2010爱思唯尔爱尔兰有限公司版权所有
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