Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

Abstract

Aims/hypothesis Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the β 2 -adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results. Materials and methods We investigated both of these variants in 7,808 unrelated, middle-aged white people for their association with obesity in a case-control study, quantitative trait analysis and meta-analysis. Moreover, both variants were investigated for their potential influence on measures of hypertension and type 2 diabetes by casecontrol and quantitative trait analyses. Results The present study did not find consistent evidence for an association of these β 2 -adrenergic receptor variants with obesity or hypertension; neither did the quantitative trait analyses show any effect of the variants on obesityrelated traits. However, both the Gly allele of the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal association with systolic blood pressure. Furthermore, there was a nominal association of the Arg16 allele frequency and genotype distribution with type 2 diabetes; however, no influence on quantitative biochemical phenotypes related to type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the metabolic syndrome was also observed (p=0.003). Logistic regression analyses provided no evidence of a synergistic or an additive effect of these variants on obesity, hypertension or diabetes. Conclusions/interpretation After studying 7,808 middleaged white subjects, we were unable to demonstrate any consistent associations between two common amino acid polymorphisms of the β 2 -adrenergic receptor and obesity, hypertension or type 2 diabetes.

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

“…Noteworthy, Arg16/Gln27 patients were on average 10 y younger, more often had an ischemic cause of their cardiomyopathy, and more often had hypertension and diabetes mellitus. Apart from the difference in age, these observations are in line with previous studies (12,32,33). The reason for the difference in age is unclear, since the Arg16/Gln27 haplotype does not influence survival in patients with HF (34) and seems not to be a risk factor for HF (35).…”

A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis

“…To avoid reporting bias, we contacted the authors for raw data. We acquired the data, including 6495 Caucasian subjects from Gjesing et al, 20 but failed to gain information from two original studies 31,32 of Asians, which included 1700 subjects altogether. These two papers both indicated 'negative' results of A46G and C79G polymorphisms, which were consistent with our results of meta-analysis in Asians and overall.…”

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]27,28 Of the 19 eligible articles, the study of Gu et al 28 was replaced by their earlier report, 10 as these two articles reported the same data. Wu et al 5 provided data on two Chinese minorities, the Hani and Yi, residents of the remote rural area of Yunnan, China.…”

“…Other studies have been unable to replicate these findings. [12][13][14][15][16][17][18][19][20] Therefore, in spite of the large number of previous reports about the association between these two polymorphisms and hypertension, the conclusion remains unclear. To clarify the effect of A46G and C79G polymorphisms on the risk of hypertension, we conducted a meta-analysis from all eligible case-control studies published to date.…”

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

“…Discordance between 938 random duplicate samples was Ͻ0.85%, and the genotyping success rate was Ͼ96%. For gene-gene interaction studies, the IRS1 Gly971Arg (rs1801278) and ADRB2 Arg16Gly and Gln27Glu (rs1042713 and rs1042714) (22) polymorphisms were also analyzed. Genotyping of the variants was performed using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.…”