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Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with

Ling Zhao1, Fan Yang, Ke Xu

  • 1Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, 5 Yiheyuan Road, Beijing, 100871, China.

Aging Cell
|October 2, 2012
PubMed

Insights

Genetic variants in the beta-2 adrenergic receptor (ADRB2) gene are linked to human longevity in men. Specific ADRB2 haplotypes influence receptor production, impacting lifespan.

Area of Science:

  • Genetics
  • Longevity Research
  • Cardiovascular Pharmacology

Background:

  • Beta-adrenoceptors are crucial pharmacological targets for cardiovascular diseases and asthma.
  • Genetic factors influencing the beta-adrenergic system affect lifespan in model organisms.
  • The association between beta-adrenergic signaling genes and human longevity remains largely unexplored.

Purpose of the Study:

  • To investigate the association between genes encoding key components of the beta-adrenergic signaling pathway and human longevity.
  • To identify specific genetic variants and haplotypes within the beta-adrenergic system that correlate with extended lifespan in a human population.

Main Methods:

  • A 10-year follow-up study involving 963 long-lived and 1028 young Han Chinese individuals.
  • Genotyping of 16 single nucleotide polymorphisms (SNPs) from ADRB1, ADRB2, ADCY5, ADCY6, and MAPK1.
  • Analysis of linkage disequilibrium and haplotype association with longevity, including translational efficiency assays in HEK293 cells.

Main Results:

  • Two SNPs in the ADRB2 gene (rs1042718 and rs1042719) were significantly associated with enhanced longevity in men.
  • The ADRB2 haplotype A-C showed an increased probability of reaching centenarian status (OR = 1.49, P = 0.0007).
  • Conversely, the C-G haplotype was associated with reduced longevity (OR = 0.63, P = 0.000018), and haplotype A-C reduced translational efficiency of the beta-2 adrenergic receptor.

Conclusions:

  • Genetic variants in ADRB2 are associated with human longevity, particularly in men.
  • The identified ADRB2 haplotypes influence receptor translational efficiency, suggesting a mechanism for lifespan modulation.
  • Enhanced production of beta-2 adrenergic receptors due to specific genetic variants is inversely associated with human lifespan.

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