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Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis.

Publication ,  Journal Article
Ni, X; Bai, C; Nie, C; Qi, L; Liu, Y; Yuan, H; Zhu, X; Sun, L; Zhou, Q; Li, Y; Zhen, H; Su, H; Li, R; Lan, R; Pang, G; Lv, Y; Zhang, W ...
Published in: Aging (Albany NY)
November 22, 2021

Genes related to human longevity have not been studied so far, and need to be investigated thoroughly. This study aims to explore the relationship among ABO gene variants, lipid levels, and longevity phenotype in individuals (≥90yrs old) without adverse outcomes. A genotype-phenotype study was performed based on 5803 longevity subjects and 7026 younger controls from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Four ABO gene variants associated with healthy longevity (rs8176719 C, rs687621 G, rs643434 A, and rs505922 C) were identified and replicated in the CLHLS GWAS data analysis and found significantly higher in longevity individuals than controls. The Bonferroni adjusted p-value and OR range were 0.013-0.020 and 1.126-1.151, respectively. According to the results of linkage disequilibrium (LD) analysis, the above four variants formed a block on the ABO gene (D'=1, r2range = 0.585-0.995). The carriers with genotypes rs687621 GG, rs643434 AX, or rs505922 CX (prange = 2.728 x 10-107-5.940 x 10-14; ORrange = 1.004-4.354) and haplotype CGAC/XGXX (p = 2.557 x 10-27; OR = 2.255) had a substantial connection with longevity, according to the results of genetic model analysis. Following the genotype and metabolic phenotype analysis, it has been shown that the longevity individuals with rs687621 GG, rs643434 AX, and rs505922 CX had a positive association with HDL-c, LDL-c, TC, TG (prange = 2.200 x 10-5-0.036, ORrange = 1.546-1.709), and BMI normal level (prange = 2.690 x 10-4-0.026, ORrange = 1.530-1.997). Finally, two pathways involving vWF/ADAMTS13 and the inflammatory markers (sE-selectin/ICAM1) that co-regulated lipid levels by glycosylation and effects on each other were speculated. In conclusion, the association between the identified longevity-associated ABO variants and better health lipid profile was elucidated, thus the findings can help in maintaining normal lipid metabolic phenotypes in the longevity population.

Duke Scholars

Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

November 22, 2021

Volume

13

Issue

22

Start / End Page

24655 / 24674

Location

United States

Related Subject Headings

  • Middle Aged
  • Male
  • Longitudinal Studies
  • Longevity
  • Lipids
  • Lipid Metabolism
  • Linkage Disequilibrium
  • Humans
  • Homeostasis
  • Glycosylation
 

Citation

APA
Chicago
ICMJE
MLA
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Ni, X., Bai, C., Nie, C., Qi, L., Liu, Y., Yuan, H., … Yang, Z. (2021). Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis. Aging (Albany NY), 13(22), 24655–24674. https://doi.org/10.18632/aging.203700
Ni, Xiaolin, Chen Bai, Chao Nie, Liping Qi, Yifang Liu, Huiping Yuan, Xiaoquan Zhu, et al. “Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis.Aging (Albany NY) 13, no. 22 (November 22, 2021): 24655–74. https://doi.org/10.18632/aging.203700.
Ni, Xiaolin, et al. “Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis.Aging (Albany NY), vol. 13, no. 22, Nov. 2021, pp. 24655–74. Pubmed, doi:10.18632/aging.203700.
Ni X, Bai C, Nie C, Qi L, Liu Y, Yuan H, Zhu X, Sun L, Zhou Q, Li Y, Zhen H, Su H, Li R, Lan R, Pang G, Lv Y, Zhang W, Yang F, Yao Y, Chen C, Wang Z, Gao D, Zhang N, Zhang S, Zhang L, Wu Z, Hu C, Zeng Y, Yang Z. Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis. Aging (Albany NY). 2021 Nov 22;13(22):24655–24674.

Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

November 22, 2021

Volume

13

Issue

22

Start / End Page

24655 / 24674

Location

United States

Related Subject Headings

  • Middle Aged
  • Male
  • Longitudinal Studies
  • Longevity
  • Lipids
  • Lipid Metabolism
  • Linkage Disequilibrium
  • Humans
  • Homeostasis
  • Glycosylation