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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Chi-Square Distribution
  • China
  • Computational Biology
  • Cross-Sectional Studies
  • Databases, Genetic
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • HLA-DQ beta-Chains / genetics*
  • Haplotypes
  • Health Status
  • Homeostasis
  • Humans
  • Lipid Metabolism / genetics*
  • Lipids / blood
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*

Substances

  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Lipids