Polymorphism of the AHSG gene is associated with increased adipocyte beta2-adrenoceptor function

Catharina Lavebratt, Elisabeth Dungner, and Johan Hoffstedt

Department of Medicine, Karolinska Institutet, Stockholm 141 86

Corresponding Author: johan.hoffstedt{at}medhs.ki.se

Background: The Alpha2 Heremans-Schmid glycoprotein (AHSG) gene is implicated in regulation of body fat and insulin sensitivity. The Met/Met genotype of the common single nucleotide polymorphism (SNP), rs4917, in the AHSG-gene has been shown associated with reduced plasma levels as well as lower body fat. Here, we studied the association of this variation with subcutaneous adipocyte lipolysis. Methods: Ninety-three obese and non-obese healthy men were genotyped for Thr230Met and subcutaneous adipose tissue biopsies were analysed for lipolysis characteristics. Results: The Met/Met-genotype was associated with a marked 1.5 log units increase in the lipolytic sensitivity to the beta2-adrenoceptor agonist terbutaline (p=0.0008) as compared to the Thr/Thr and Thr/Met-genotypes. This corresponds to approximately a 35-fold increase in beta2-adrenoceptor function. The genotype effect was independent of body mass index and waist circumference. In contrast, lipolytic sensitivity to both the beta1-adrenoceptor agonist dobutamine (p=0.25) and the alpha2A-adrenoceptor agonist clonidine (p=0.54) was unaffected by the Thr230Met variation. Moreover, no difference in either maximal stimulation or inhibition of lipolysis was found between genotypes. Conclusions: A common variation (Thr230Met) in the AHSG gene is associated with a marked increase in beta2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation.

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