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Aging (Albany NY). 2017 Nov 10;9(11):2316-2333. doi: 10.18632/aging.101323.

Identification of new genetic variants of HLA-DQB1 associated with human longevity and lipid homeostasis-a cross-sectional study in a Chinese population.

Author information

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.

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.

KEYWORDS:

Chinese population; HLA-DQB1; human longevity; lipid phenotypes

PMID:
29129831
PMCID:
PMC5723689
DOI:
10.18632/aging.101323
[Indexed for MEDLINE]
Free PMC Article

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