Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels

Abstract

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The b 2 adrenergic receptor (b 2 -AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between b 2 -AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the b 2 -AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5 0 LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the b 2 -AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5 0 LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5 0 LC-Arg19 homozygous (P ¼ 0.03 and P ¼ 0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P ¼ 0.02 and P ¼ 0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P ¼ 0.01 and P ¼ 0.03, respectively).

β-AR Polymorphisms and Glycemic and Lipid Parameters in Hypertensive Individuals Receiving Carvedilol or Metoprolol

“…22 Obese Spanish men with the Glu27Glu genotype had higher 2 hour post-load glucose concentrations compared with the Gln27Gln genotype. 23 Some studies also have found an association between the Gln allele and higher triglycerides concentrations, 25,26 while other investigators did not find an association between β2-AR and lipid levels. 27-29 …”

Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context

“…Then the models were adjusted for such potential effect-mediators as systolic (SBP) and diastolic (DBP) blood pressures (mm Hg), smoking (ever smoked), diabetes, body-mass index (BMI; kg/m 2 ), total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol (mg/100 ml) (Jalba et al, 2008; Petrone et al, 2006; Pinelli et al, 2006; Puddu et al, 2007). The absolute values of SBP, DBP, TC, and HDL were used in the regression models with increments of 10 mm Hg for SBP and DBP, and 10 mg/100 ml for TC and HDL cholesterol.…”

Pharmacogenetics of the human beta-adrenergic receptors

“…In a larger study of 642 overweight or obese subjects, ADRB2 Haplotype 1 predicted increased levels of triglycerides and LDL-cholesterol (the Thr164Ile polymorphism was not genotyped in this work). 89 The largest ADRB2 haplotype study to date involved genotyping of 523 patients who had myocardial infarction from a prospectively followed cohort of 14 916 initially healthy American men. Four controls (n ¼ 2092) were matched for each case and Haplotype 4 and the combined group of Haplotypes 1 and 3 had significantly altered risk of myocardial infarction with odds ratios of 0.178 (95% CI: 0.043-0.737; P ¼ 0.017) and 1.235 (95% CI: 1.031-1.480; P ¼ 0.022) respectively (the Cys-19Arg polymorphism was not genotyped in this work).…”