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 beta3-adrenergic receptor gene is associated with obesity (relative risk approximately 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 -adrenoceptor. The genetic allele variance influences also the native receptor function when measured in isolated human fat cells. The human beta2-adrenoceptor gene shows a high degree of polymorphism. The role of beta2-receptor gene polymorphism for obesity has so far only been investigaed in women. A Gln27Glu variant is markedly associated with obesity with a relative risk for obesity of approximately 7 and odds ratio of approximately 10. Women who are homozygous for 27Glu have approximately 20 kg higher fat mass than controls. Thus, polymorphism in genes coding for different beta-adrenoceptor subtypes may be important for the development of human obesity.