Adrenoceptor genes in human obesity

The genes causing obesity in rodent models have been characterized, but do not seem to be important for human obesity. Recently the putative association between obesity and polymorphism in human beta-adrenergic receptor genes have been studied intensely in the light of the important role of these receptors in the regulation of energy mobilization and utilization, A polymorphism (Trp64Arg) in the beta(3)-adrenergic receptor gene is associated with obesity (relative risk approximate to 2) in some but not all investigations on Caucasian and Japanese populations, When expressed in artificial cell systems, the polymorphism is associated with alterations of the beta(3)-adrenoceptor. The genetic allele variance influences also the native receptor function when measured in isolated human fat cells. The human beta(2)-adrenoceptor gene shows a high degree of polymorphism. The role of beta(2)-receptor gene polymorphism for obesity has so far only been investigated in women. A Gln27Glu variant is markedly associated with obesity with a relative risk for obesity of approximate to 7 and odds ratio of approximate to 10. Women who are homozygous for 27Glu have approximate to 20 kg higher fat mass than controls. Thus, poly morphism in genes coding for different beta-adrenoceptor subtypes may be important for the development of human obesity.