β 3-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women

Abstract

We investigated gender differences in the relationships between the Trp64Arg variant of the β 3-adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the β 3-AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the β 3-AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the β 3-AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index ≥24.2 kg/m 2), with the β 3-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation . In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the β 3-AR gene variant either in the obese and non-obese group. We suggest that the β 3-AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the β 3-AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.