Mutations in the β1 adrenergic receptor gene and massive obesity in Japanese

Catecholamines strongly promote lipolysis and thermogenesis, and play a central role in the regulation of body fat content. The β1 adrenergic receptor (BAR-1) is a major mediator of catecholamine-induced lipolysis and thermogenesis. To explore whether mutations in the BAR-1 gene contribute to morbid obesity in Japanese, we scanned for mutations in the coding sequence of the gene in 50 morbid obese [body mass index (BMI) ≧ 35.0 kg/m2; 99.7th percentile] Japanese subjects. Direct DNA sequencing was performed following polymerase chain reaction (PCR) amplification. Two common polymorphisms, Gly49Arg and Arg389Ser, were detected in these subjects. The frequencies of these polymorphisms, as determined by PCR-restriction fragment length polymorphism (RFLP) analysis, showed no significant difference between 180 severely obese subjects (BMI ≧ 30.0 kg/m2; 97th percentile) and 132 control (BMI < 25.0 kg/m2) subjects. This study represents the first investigations of genetic variations of BAR-1 in relationship to morbid obesity and suggests mutations in the BAR-1 coding sequence is not likely a major cause of morbid obesity at least in Japanese.