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

Publication ,  Journal Article
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, BK; Suh, Y; Zeng, Y; Tian, X-L
Published in: Aging Cell
December 2012

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.

Duke Scholars

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Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

December 2012

Volume

11

Issue

6

Start / End Page

1094 / 1101

Location

England

Related Subject Headings

  • Transfection
  • Surveys and Questionnaires
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Protein Biosynthesis
  • Polymorphism, Single Nucleotide
  • Mitogen-Activated Protein Kinase 1
  • Male
  • Luciferases, Renilla
  • Longevity
 

Citation

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Zhao, L., Yang, F., Xu, K., Cao, H., Zheng, G.-Y., Zhang, 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
Zhao, Ling, Fan Yang, Ke Xu, Huiqing Cao, Gu-Yan Zheng, Yan Zhang, Jianxin Li, et al. “Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity.Aging Cell 11, no. 6 (December 2012): 1094–1101. https://doi.org/10.1111/acel.12011.
Zhao L, Yang F, Xu K, Cao H, Zheng G-Y, Zhang Y, et al. Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity. Aging Cell. 2012 Dec;11(6):1094–101.
Zhao, Ling, et al. “Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity.Aging Cell, vol. 11, no. 6, Dec. 2012, pp. 1094–101. Pubmed, doi:10.1111/acel.12011.
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 BK, Suh Y, Zeng Y, Tian X-L. Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity. Aging Cell. 2012 Dec;11(6):1094–1101.
Journal cover image

Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

December 2012

Volume

11

Issue

6

Start / End Page

1094 / 1101

Location

England

Related Subject Headings

  • Transfection
  • Surveys and Questionnaires
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Protein Biosynthesis
  • Polymorphism, Single Nucleotide
  • Mitogen-Activated Protein Kinase 1
  • Male
  • Luciferases, Renilla
  • Longevity