Common genetic variants of the ?2-adrenergic receptor affect its translational efficiency and are associated with human longevity
Language: 
English
Abstract: 

?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-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 ?2-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 ?2-adrenergic receptors caused by genetic variants is inversely associated with human lifespan.

Author(s): 
Zhao, Ling
Yang, Fan
Xu, Ke
Cao, Huiqing
Zheng, Gu-Yan
Zhang, Yan
Li, Jianxin
Cui, Hanbin
Chen, Xiaomin
Zhu, Zhiming
He, Hongbo
Mo, Xianming
Kennedy, Brian K.
Suh, Yousin
Zeng, Yi
Tian, Xiao-Li
Item Type: 
Journal Article
Publication Title: 
Aging Cell
Journal Abbreviation: 
Aging Cell
Publication Date: 
2012-12
Publication Year: 
2012
Pages: 
1094-1101
Volume: 
11
Issue: 
6
ISSN: 
1474-9726
DOI: 
10.1111/acel.12011
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23020224 PMCID: PMC3633790

Turabian/Chicago Citation

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 and Xiao-Li Tian. 2012-12. "Common genetic variants of the ?2-adrenergic receptor affect its translational efficiency and are associated with human longevity." Aging Cell 11: 6: 1094-1101. 10.1111/acel.12011.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/acel.12011 | issn = 1474-9726 | volume = 11 | pages = 1094-1101 | last = Zhao | first = Ling | coauthors = Yang, Fan, Xu, Ke, Cao, Huiqing, Zheng, Gu-Yan, Zhang, Yan, Li, Jianxin, Cui, Hanbin, Chen, Xiaomin, Zhu, Zhiming, He, Hongbo, Mo, Xianming, Kennedy, Brian K., Suh, Yousin, Zeng, Yi, Tian, Xiao-Li | title = Common genetic variants of the ?2-adrenergic receptor affect its translational efficiency and are associated with human longevity | journal = Aging Cell | date = 2012-12 | pmid = | pmc = }} </ref>