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

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Abstract
Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The β2 adrenergic receptor (β2-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 β2-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 β2-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′LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the β2-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′LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19 homozygous (P=0.03 and P=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=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5′LC-Cys19Arg16Gln27 haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19Gly16Glu27 haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5′LC-Cys19Arg16Gln27 haplotype.