Research Paper|Volume 12, Issue 17|pp 16775—16802

Identification of cardiovascular health gene variants related to longevity in a Chinese population

Li Zhang^1,², Chen Bai³, Chao Nie⁴, Xiaoquan Zhu¹, Huiping Yuan¹, Liang Sun¹, Qi Zhou¹, Xiaoling Li², Xuan Xian⁵, Fan Yang^6,^7,⁸, Guofang Pang⁹, Yuan Lv⁹, Xiaolin Ni^1,², Caiyou Hu⁹, Ze Yang^1,²

¹The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China
²Graduate School of Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China
³School of Labor and Human Resources, Renmin University, Beijing, P.R. China
⁴BGI-Shenzhen, Shenzhen, Guangdong, P.R. China
⁵iCarbonX Company Limited, Shenzhen, Guangdong, P.R. China
⁶Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
⁷Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
⁸Key Laboratory of Embryo Molecular Biology, National Health Commission and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, P.R. China
⁹Department of Neurology, Jiangbin hospital, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, P.R. China

Received: January 11, 2020Accepted: May 25, 2020Published: September 7, 2020

https://doi.org/10.18632/aging.103396

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cardiovascular disease (CVD) is one of the most important causes of human death, but no attention has been paid to cardiovascular health genes related to healthy longevity. Therefore, we developed a cohort study to explore such genes in healthy, long-lived Chinese subjects. A total of 13275 healthy elderly people were enrolled, including 5107 healthy long-lived individuals and 8168 age-matched control individuals with low CVD risk. Using a combination of whole-exome sequencing (WES) and genome-wide association studies (GWAS), we identified 2 genetic variants (TFPI rs7586970 T, p=0.013, OR=1.100. ADAMTS7 rs3825807 A, p=0.017, OR=1.198) associated with healthy lipid metabolism and longevity. Furthermore, we showed that an interaction among TFPI rs7586970, ADAMTS7 rs3825807 and APOE ɛ3 maintained normal blood lipid levels in centenarians by stratified analysis of CVD risk factors. Finally, through biological function analysis, we revealed clues regarding the mechanism of factor related to cardiovascular health (FCH) such as lipids and longevity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the two variants above may be associated with longevity via FCH lipid metabolism pathways. From a meta-analysis of venous thrombosis patients, we unexpectedly found that rs7586970 T is associated with both longevity and protection against vascular disease.