THE TRP64ARG MUTATION OF THE BETA-3 ADRENERGIC-RECEPTOR GENE HAS NO EFFECT ON OBESITY PHENOTYPES IN THE QUEBEC FAMILY STUDY AND SWEDISH OBESE SUBJECTS COHORTS

The beta adrenergic system plays a key role in regulating energy balan ce through the stimulation of both thermogenesis and lipid mobilizatio n in brown and white adipose tissues in human and various animal model s, Recent studies have suggested that a missense Trp64Arg mutation in the beta 3 adrenergic receptor (ADRB3) gene was involved in obesity an d insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Quebec Family Study (QFS) and the Swedish Obese Subjects (SOS), In QFS, no association wa s found between this mutation and body mass index (BMI), body fat incl uding abdominal visceral fat, resting metabolic rate, various diabetes and cardiovascular risk factors, and changes in body weight and body fat over a 12-yr period. With the exception of RMR (P=0.04), no eviden ce of linkage was detected between the mutation and phenotypes of QFS based on sib-pair data. In SOS, the frequency of the Trp64Arg allele w as not significantly different between nonobese and obese female subje cts and no association was found between the mutation and body weight gain over time. These findings do not support the view that there is a n association between the Trp64Arg mutation in the ADRB3 gene and obes ity.