1. ¹Endocrinology, Department of Clinical Sciences, University 'La Sapienza', Rome, Italy
2. ²Center for Nutrition and Dietetics of the Department of Paediatrics, University 'La Sapienza', Rome, Italy
3. ³Diabetes Unit, IRCCS INRCA, Rome, Italy

Correspondence: Professor R Buzzetti, Endocrinology, Department of Clinical Sciences, University of Rome 'La Sapienza', Viale del Policlinico 155, 00161, Rome, Italy. Tel: +39 06 4478392; Fax +39 06 4469190; E-mail: raffaella.buzzetti@uniroma1.it

Received 7 December 2004; Revised 26 July 2005; Accepted 22 September 2005; Published online 26 October 2005.

Abstract

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The ₂ adrenergic receptor (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 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 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'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the 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'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.