SummaryThe aim of this study was to determine whether there was an association between body fat distribution, blood lipid profiles, and ␤ 3 -adrenergic receptor gene polymorphism in Korean middle-aged women. Subjects were grouped according to BMI as obese ( Ն 25 BMI, n ϭ 95) or non-obese (BMI Ͻ 25, n ϭ 93). The Trp64Arg mutation of the ␤ 3 -adrenergic receptor gene was detected by PCR-RFLP. Skinfold thickness, body circumference, intra-abdominal fat area by CT, and blood lipid profiles were also measured. Data were compared using ANOVA, Bonferroni t -test, and Chi-square. Significance for statistical analyses were set at p Ͻ 0.05. In the obese group, 63.16% were Trp64Trp homozygotes and 36.84% were Trp64Arg heterozygotes, compared to 80.65% who were Trp64Trp homozygotes and 19.35% who were Trp64Arg heterozygotes in the non-obese group. These results indicated a significant ( 2 ϭ 4.943, p Ͻ 0.05) difference between the two groups. Frequency of the Arg64 allele in the obese group (16.84%) showed a significant ( 2 ϭ 4.185, p Ͻ 0.05) difference as compared to the non-obese group (9.68%). Skinfold thickness and body circumference of the Trp64Arg heterozygote group showed a consistent increase as compared to the Trp64Trp homozygote group. Visceral fat area and VSR of Trp64Arg heterozygote group showed a higher tendency than Trp64Trp homozygotes in the obese group, but these differences were not statistically significant. In conclusion, the Trp64Arg polymorphism of the ␤ 3 -adrenergic receptor gene is associated with obesity in middle-aged Korean women, but it is difficult to suggest the prominent association of the Trp64Arg polymorphism of the ␤ 3 -adrenergic receptor gene with prevalence of abdominal obesity or dyslipidemia in Korean middle-aged women. Key Words obesity, ␤ 3 -adrenergic receptor gene, Trp64Arg polymorphism, body fat distribution The obese phenotype is under the control of genetic and environmental influences. Much insight has been gained regarding obesity-related genetic factors ( 1 ), and the advent of advanced molecular biological techniques has accelerated the search for the specific genes influencing human obesity. Several candidate genes have been associated with energy expenditure, body fat distribution, and lipid metabolism ( 2 ). Among these genes, the ␤ 3 -adrenergic receptor gene regulates lipolysis in adipose tissue, and contributes to population variations in energy expenditure and body fat distribution ( 3 ). The ␤ 3 -adrenergic receptor is quite different from ␤ 1 and ␤ 2 receptor subtypes in that it is relatively resistant to desensitization and may maintain signaling during periods of sustained sympathetic stimulation ( 4 ). A missense mutation of the ␤ 3 -adrenergic receptor gene, results in replacement of tryptophan by arginine at codon 64 (Trp64Arg). This single nucleotide polymorphism (SNP) has been associated with morbid obesity and insulin resistance ( 5 ). The Trp64Arg polymorphism in the ␤ 3 -adrenergic receptor gene was shown to be associated decreased energy expenditure in P...