Research Paper Volume 9, Issue 11 pp 2316—2333
Identification of new genetic variants of HLA-DQB1 associated with human longevity and lipid homeostasis—a cross-sectional study in a Chinese population
- 1 The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China
- 2 Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- 3 Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC 27708, USA
- 4 Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China
- 5 BGI-Shenzhen, Shenzhen, Guangdong, China
- 6 Jiangbing Hospital, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
- 7 Office of Longevity Cultural, People's Government of Yongfu County, Yongfu, Guangxi, China
- 8 Birth Defects Prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, China
- 9 Genetic Testing Center Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China
- 10 Department of Obstetrics and Gynecology, Aviation General Hospital of China Medical University, Beijing, China
- 11 Capital Medical University Affiliated Beijing Ditan Hospital, Beijing, China
Received: September 1, 2017 Accepted: November 2, 2017 Published: November 10, 2017 Corrected online: March 15, 2018
https://doi.org/10.18632/aging.101323How to Cite
Abstract
Healthy longevity has been an unremitting pursuit of human, but its genetic and the environment causes are still unclear. As longevity population is a good healthy aging model for understanding how the body begin aging and the process of aging, and plasma lipids metabolism and balance is a very important to life maintain and physiologic functional turnover. It is important to explore how the effect of genetic variants associated long-life individuals on lipids metabolism and balance. Therefore, we developed a comparative study based population which contains 2816 longevity and 2819 control. Through whole-exome sequencing and sanger sequencing genotypes, we identified four new single nucleotide polymorphisms of HLA-DQB1(major histocompatibility complex, class II, DQ beta 1), rs41542812 rs1049107 rs1049100 rs3891176(Prange=0.048-2.811×10-8 for allele frequencies), associated with longevity in Chinese Longevity Cohort. Further, by analysis of the longevity-variants linked to blood lipids, we identified HLA-DQB1 rs1049107, T-carriers (PHDL=0.006, OR: 11.277; PTG=9.095×10-7, OR: 0.025; PLDL/HDL=0.047, OR: 1.901) and HLA-DQB1 rs1049100, T-carriers (PTG=1.799×10-6, OR: 0.028) associated with lipid homeostasis in long lived individuals. Our finding showed that longevity and lipid homeostasis were associated with HLA-DQB1 and suggested that immune gene variants could act on both new function of maintaining the homeostasis and anti-aging in longevity.