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


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.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC3633790 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Zhao Ling L   Yang Fan F   Xu Ke K   Cao Huiqing H   Zheng Gu-Yan GY   Zhang Yan Y   Li Jianxin J   Cui Hanbin H   Chen Xiaomin X   Zhu Zhiming Z   He Hongbo H   Mo Xianming X   Kennedy Brian K BK   Suh Yousin Y   Zeng Yi Y   Tian Xiao-Li XL  

Aging cell 20121011 6


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 10  ...[more]

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