Mutant rs189037 in the Ataxia-Telangiectasia Mutated Gene Significantly Associates With Ventricular Thickness and Human Lifespan

Background: This study intend for the first time to determine whether the associations of rs189037 in the ataxia-telangiectasia mutated (ATM) gene with cardiac structure and human longevity exist. Methods: Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan, this study enrolled 547 centenarians, 250 young aged 20-45 years and 250 middle-aged and elderly aged 46-90 years. Results: Frequency of TT genotype was higher in the middle-aged and elderly than those in the young and centenarians (P 0.05 for all). In both the middle-aged and elderly and centenarians, TT genotype was positively associated with interventricular septum thickness, left ventricular posterior wall thickness and left ventricular end diastolic diameter (P<0.05 for all). Conclusion: This study demonstrated that more commonly identified in the middle-aged and elderly than the young and centenarians, mutant rs189037 in the ATM gene is significantly associated with increased LV thickness and volume and might induce LV eccentric hypertrophy and shorten human lifespan. Rs189037 without mutation might be an indicator of youth health and successful aging, whereas mutant rs189037 might avoid successful aging and hinder human longevity. Funding Statement: This work was supported by grants from the National Key R&D Program of China (2016YFC0105006, 2018YFC2000400), the National Natural Science Foundation of China (81900357, 82001476, 81903392, 81941021), the National S&T Resource Sharing service platform Project of China (YCZYPT[2018]07), the General Hospital of PLA Medical Big Data R&D Project (MBD2018030), the China Postdoctoral Science Foundation funded project (2019M650359), the National Geriatric Disease Clinical Medicine Research Center Project (NCRCG-PLAGH-2017-014), the Military Medical Science and Technology Youth Incubation Program (20QNPY110), the Hainan Medical and Health Research Project (16A200057), the Sanya Medical and Health Science and Technology Innovation Project (2016YW21, 2017YW22, 2018YW11), the Military Medicine Youth Program of Chinese PLA General Hospital (QNF19069) and the Clinical Scientific Research Supporting Fund of Chinese PLA General Hospital (2017FC-CXYY-3009). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The current study was carried out based on the approval of the Ethics Committee of the Hainan Hospital of the Chinese People’s Liberation Army General Hospital (Sanya, Hainan; Number: 301hn11201601). All participants provided written informed consent prior to the start of this study.