Open AccessCommon genetic variants of the β2‐adrenergic receptor affect its translational efficiency and are associated with human longevity
Author(s) -
Zhao Ling,
Yang Fan,
Xu Ke,
Cao Huiqing,
Zheng GuYan,
Zhang Yan,
Li Jianxin,
Cui Hanbin,
Chen Xiaomin,
Zhu Zhiming,
He Hongbo,
Mo Xianming,
Kennedy Brian K.,
Suh Yousin,
Zeng Yi,
Tian XiaoLi
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12011
Subject(s) - longevity , biology , haplotype , linkage disequilibrium , snp , single nucleotide polymorphism , genetics , β2 adrenergic receptor , adrenergic receptor , medicine , endocrinology , allele , gene , genotype , receptor , agonist
Summary 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 C hinese longitudinal healthy longevity survey. The H an C hinese population in this study consisted of 963 long‐lived and 1028 geography‐matched young individuals. Sixteen SNP s from ADRB 1 , ADRB 2 , ADCY 5 , ADCY 6 , and MAPK 1 were selected and genotyped. Two SNP s, rs1042718 ( C/A ) and rs1042719 ( G/C ), of ADRB 2 in linkage disequilibrium (D' = 1.0; r 2 = 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. ADRB 2 encodes the β2‐adrenergic receptor; the haplotype A‐C markedly reduced its translational efficiency compared with C‐G ( P = 0.002) in transfected HEK 293 cells. Thus, our data indicate that enhanced production of β2‐adrenergic receptors caused by genetic variants is inversely associated with human lifespan.