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), 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 > or = 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 beta 3-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.
Kurabayashi
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T
Garvan Insitute of Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
Carey
D G
DG
Morrison
N A
NA
D000368:Aged; D000595:Amino Acid Sequence; D001120:Arginine; D001794:Blood Pressure; D015992:Body Mass Index; D001835:Body Weight; D015331:Cohort Studies; D017931:DNA Primers; D003971:Diastole; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D008572:Menarche; D008593:Menopause; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D010298:Parity; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3; D012098:Reproduction; D012727:Sex Characteristics; D013599:Systole; D013851:Thinness; D014364:Tryptophan
D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D014364:Tryptophan; D001120:Arginine