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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

Fan Yang1,2, Liang Sun1, Xiaoquan Zhu1, Jing Han1,2, Yi Zeng3,4, Chao Nie5, Huiping Yuan1, Xiaoling Li1,2, Xiaohong Shi1, Yige Yang1, Caiyou Hu6, Zeping Lv6, Zezhi Huang7, Chenguang Zheng8, Siying Liang9, Jin Huang10, Gang Wan11, Keyan Qi1, Bin Qin1, Suyan Cao1, Xin Zhao1, Yongqiang Zhang1, Ze Yang1,2
  • 1The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China
  • 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • 3Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC 27708, USA
  • 4Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China
  • 5BGI-Shenzhen, Shenzhen, Guangdong, China
  • 6Jiangbing Hospital, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
  • 7Office of Longevity Cultural, People's Government of Yongfu County, Yongfu, Guangxi, China
  • 8Birth Defects Prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, China
  • 9Genetic Testing Center Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China
  • 10Department of Obstetrics and Gynecology, Aviation General Hospital of China Medical University, Beijing, China
  • 11Capital Medical University Affiliated Beijing Ditan Hospital, Beijing, China
Received: September 1, 2017Accepted: November 2, 2017Published: November 10, 2017
https://doi.org/10.18632/aging.101323

Copyright: © 2017 Yang 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

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.