Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg Polymorphism of the β3-Adrenergic Receptor Is Associated With Type 2 Diabetes and Obesity in a Large Japanese Sample

Abstract

OBJECTIVE -Despite a large number of studies, no association of the Trp64Arg polymorphism of the ␤ 3 -adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample.RESEARCH DESIGN AND METHODS -A total of 1,685 subjects (935 women and 750 men, aged 58.7 Ϯ 12.4 years) from a cohort population (n ϭ 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n ϭ 1,155), Trp/Arg (n ϭ 486), and Arg/Arg (n ϭ 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI Ն30 kg/m 2 were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The 2 test and analysis of variance were used for the association studies and to assess the differences in the traits' values, respectively.RESULTS -More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P Ͻ 0.001; and 4.16%, P ϭ 0.007, respectively) or genotype Trp/Arg (2.06%, P Ͻ 0.001; and 5.97%, P ϭ 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 Ϯ 7.95 vs. 25.93 Ϯ 7.21, P ϭ 0.038) and BMI (25.07 Ϯ 3.84 vs. 23.63 Ϯ 3.18, P ϭ 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups.CONCLUSIONS -Genotype Arg/Arg, but not Trp/Arg, of the ␤ 3 -adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

“…24 In previous epidemiologic studies, the association between the ADRB3 variant and obesity-related phenotypes has been investigated among individuals from several racial/ ethnic groups and nationalities, including Caucasians, 13 Japanese, 12,25,26 Pima Indians, 24 Mexican Americans, 14 African Americans 27,28 and Jamaicans. 29 Previous studies of white or Japanese populations found the variant allele of the ADRB3 receptor to be associated with elevated measures of obesity, 13 whereas two previous studies of African Americans reported associations with the wild-type receptor.…”

“…11 The ADRB3 gene is highly conserved between humans and rodents and its functional impairment may lead to obesity by altering metabolic processes of fat tissue. 11,12 The receptor is expressed in visceral and subcutaneous fat tissue, but is more abundant and active in visceral tissue. 11 A missense change at codon 64 of this gene (Trp64Arg) has been identified and has been associated with measures of obesity, [12][13][14] weight gain, 15 insulin resistance 13 and type II diabetes.…”

“…11,12 The receptor is expressed in visceral and subcutaneous fat tissue, but is more abundant and active in visceral tissue. 11 A missense change at codon 64 of this gene (Trp64Arg) has been identified and has been associated with measures of obesity, [12][13][14] weight gain, 15 insulin resistance 13 and type II diabetes. 12 In the current study, we examined the association between the codon 64 ADRB3 missense change and measures of weight and obesity among African-American breast cancer patients.…”

“…11 A missense change at codon 64 of this gene (Trp64Arg) has been identified and has been associated with measures of obesity, [12][13][14] weight gain, 15 insulin resistance 13 and type II diabetes. 12 In the current study, we examined the association between the codon 64 ADRB3 missense change and measures of weight and obesity among African-American breast cancer patients. We assessed the relationship of the ADRB3 genotypes with visceral and subcutaneous abdominal fat, body mass index (BMI), weight change and measures of central obesity (waist, hip, waist-to-hip ratio (WHR)) approximately 30 months after diagnosis of breast cancer, when most women had finished their primary cancer treatment.…”

.BETA.2- and .BETA.3-Adrenoceptor Polymorphisms Relate to Subsequent Weight Gain and Blood Pressure Elevation in Obese Normotensive Individuals

“…Two polymorphisms in the β2-adrenergic receptors (arginine/glycine substitution, Arg16Gly; and glutamine/ glutamate substitution, Gln27Glu) of the β2-adrenoceptor gene were studied (6,7). One polymorphism (tryptophan/ arginine substitution, Trp64Arg) of the β3-adrenoceptor gene was also studied (10).…”