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

Ling Zhao, Fan Yang, Ke Xu, Huiqing Cao, Gu Yan Zheng, Yan Zhang, Jianxin Li, Hanbin Cui, Xiaomin Chen, Zhiming Zhu, Hongbo He, Xianming Mo, Brian K. Kennedy, Yousin Suh, Yi Zeng, Xiao Li Tian

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

β-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of β-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the β-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals. Sixteen SNPs from ADRB1, ADRB2, ADCY5, ADCY6, and MAPK1 were selected and genotyped. Two SNPs, rs1042718 (C/A) and rs1042719 (G/C), of ADRB2 in linkage disequilibrium (D' = 1.0; r2 = 0.67) were found to be associated with enhanced longevity in men in two geographically isolated populations. Bonferroni-corrected P-values in a combined analysis were 0.00053-0.010. Men with haplotype A-C showed an increased probability to become centenarians (the frequency of A-C in long-lived and young individuals are 0.332 and 0.250, respectively, OR = 1.49, CI 95% = 1.17-1.88, P = 0.0007), in contrast to those with haplotype C-G (the frequency of C-G in long-lived and young individuals are 0.523 and 0.635, respectively, OR = 0.63, CI 95% = 0.51-0.78, P = 0.000018). The permuted P-values were 0.00005 and 0.0009, respectively. ADRB2 encodes the β2-adrenergic receptor; the haplotype A-C markedly reduced its translational efficiency compared with C-G (P = 0.002) in transfected HEK293 cells. Thus, our data indicate that enhanced production of β2-adrenergic receptors caused by genetic variants is inversely associated with human lifespan.

Original languageEnglish (US)
Pages (from-to)1094-1101
Number of pages8
JournalAging cell
Volume11
Issue number6
DOIs
StatePublished - Dec 1 2012

Keywords

  • Haplotype
  • Longevity
  • Single nucleotide polymorphism
  • Translational efficiency
  • β2-adrenergic receptor

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Zhao, L., Yang, F., Xu, K., Cao, H., Zheng, G. Y., Zhang, Y., Li, J., Cui, H., Chen, X., Zhu, Z., He, H., Mo, X., Kennedy, B. K., Suh, Y., Zeng, Y., & Tian, X. L. (2012). Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity. Aging cell, 11(6), 1094-1101. https://doi.org/10.1111/acel.12011