Yang Fan, Sun Liang, Zhu Xiaoquan, Han Jing, Zeng Yi, Nie Chao, Yuan Huiping, Li Xiaoling, Shi Xiaohong, Yang Yige, Hu Caiyou, Lv Zeping, Huang Zezhi, Zheng Chenguang, Liang Siying, Huang Jin, Wan Gang, Qi Keyan, Qin Bin, Cao Suyan, Zhao Xin, Zhang Yongqiang, Yang Ze
The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Aging (Albany NY). 2017 Nov 10;9(11):2316-2333. doi: 10.18632/aging.101323.
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(=0.048-2.811×10 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 (=0.006, OR: 11.277; =9.095×10, OR: 0.025; =0.047, OR: 1.901) and HLA-DQB1 rs1049100, T-carriers (=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.
健康长寿一直是人类不懈的追求，但其遗传和环境成因仍不明确。由于长寿人群是理解身体如何开始衰老以及衰老过程的良好健康衰老模型，而血浆脂质代谢与平衡对于维持生命和生理功能更新非常重要。探索与长寿个体相关的基因变异对脂质代谢与平衡的影响很重要。因此，我们开展了一项基于人群的比较研究，其中包括2816名长寿者和2819名对照者。通过全外显子组测序和桑格测序基因分型，我们在中国长寿队列中鉴定出与长寿相关的HLA - DQB1（主要组织相容性复合体，II类，DQβ1）的四个新单核苷酸多态性，rs41542812、rs1049107、rs1049100、rs3891176（等位基因频率为0.048 - 2.811×10）。此外，通过分析与血脂相关的长寿变异，我们鉴定出与长寿个体脂质稳态相关的HLA - DQB1 rs1049107，T携带者（P = 0.006，OR：11.277；P = 9.095×10，OR：0.025；P = 0.047，OR：1.901）和HLA - DQB1 rs1049100，T携带者（P = 1.799×10 - 6，OR：0.028）。我们的研究结果表明，长寿和脂质稳态与HLA - DQB1相关，并提示免疫基因变异可能在维持稳态和长寿抗衰老的新功能中发挥作用。
