THE BETA-3-ADRENERGIC RECEPTOR GENE TRP64ARG MUTATION IS OVERREPRESENTED IN OBESE WOMEN - EFFECTS ON WEIGHT, BMI, ABDOMINAL FAT, BLOOD-PRESSURE, AND REPRODUCTIVE HISTORY IN AN ELDERLY AUSTRALIAN POPULATION

A tryptophan to arginine (Trp64Arg) mutation in the beta 3-adrenergic receptor (beta 3-AR) gene has been implicated in diabetes and obesity. We investigated the relationship of the beta 3-AR gene mutation with total body weight, BMI, central abdominal fat, blood pressure (BP), an d reproductive history in 686 elderly subjects (429 women, 257 men; me an age 69.8 +/- 6.9 [+/- SD] years) from a cross section of a normal p opulation in Australia. About 14% of the test population were heterozy gote carriers of the Trp64Arg mutation; however, significant effects o n clinical parameters were only observed in women. The frequency of th e mutation was significantly increased in obese women compared with le an women (BMI greater than or equal to 27: 20% compared with BMI <27: 11%, P = 0.02). Significantly higher total body weight (67.5 +/- 12.9 vs. 64.1 +/- 12.2 kg, P = 0.03) and BMI (26.3 +/- 4.7 vs. 25.1 +/- 4.5 kg/m(2), P = 0.03) was observed in heterozygote women compared with n ormal subjects (homozygous for tryptophan). Central abdominal fat was not significantly different, except in women under 70 years, where het erozygotes had 16% higher abdominal fat compared with normal subjects. Female heterozygotes had significantly higher diastolic BP, even afte r adjustment for age and BMI (88.9 +/- 11.1 vs. 84.2 +/- 10.8 mmHg, P = 0.003) and a longer reproductive life, with an earlier menarche (12. 8 +/- 1.3 vs. 13.4 +/- 1.5 years, P = 0.006), a higher gravidity (4.4 +/- 2.4 vs. 3.5 +/- 2.1, P = 0.01), and higher parity (3.8 +/- 2.0 vs. 3.0 +/- 1.9, P = 0.005). Clearly, the beta 3-AR mutation has pleiotro phic effects on a number of physiological systems, including BMI, BP, and reproductive history, perhaps suggesting evolutionary reasons for its maintenance in the population.