The β3-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

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Abstract
A tryptophan to arginine (Trp64Arg) mutation in the β3-adrenergic receptor (β3-AR) gene has been implicated in diabetes and obesity. We investigated the relationship of the β3-AR gene mutation with total body weight, BMI, central abdominal fat, blood pressure (BP), and reproductive history in 686 elderly subjects (429 women, 257 men; mean age 69.8 ± 6.9 [±SD] years) from a cross section of a normal population in Australia. About 14% of the test population were heterozygote carriers of the Trp64Arg mutation; however, significant effects on clinical parameters were only observed in women. The frequency of the mutation was significantly increased in obese women compared with lean women (BMI ≥ 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/m2, P = 0.03) was observed in heterozygote women compared with normal subjects (homozygous for tryptophan). Central abdominal fat was not significantly different, except in women under 70 years, where heterozygotes had 16% higher abdominal fat compared with normal subjects. Female heterozygotes had significantly higher diastolic BP, even after 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 β3-AR mutation has pleiotrophic effects on a number of physiological systems, including BMI, BP, and reproductive history, perhaps suggesting evolutionary reasons for its maintenance in the population.

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