¹Clinical Pharmacology and Metabolic Research Unit, Department of Medicine, University of Vermont, Burlington, Vermont, USA

²Division of Endocrinology, Diabetes and Nutrition, and Baltimore Veterans Administration Geriatric Research and Education Clinical Center, Department of Medicine, University of Maryland, Baltimore, Maryland, USA

Correspondence to: E T Poehlman, Given Building C-247, College of Medicine, University of Vermont, Burlington, VT 05405, USA. E-mail: epoehlma@zoo.uvm.edu

^a†Present address: Research Center on Aging, Geriatric Institute of University of Sherbrooke, 1036 Belvédère Sud, Sherbrooke, Québec, Canada, J1H 4C4.

^b‡Present address: Département de Nutrition, Faculté de Médecine, Université de Montréal, Montréal, Qué, Canada, H3T 1A8.

Introduction: Genetic variants affecting adrenoceptors have been suggested to influence body fatness. A putative gain-of-function polymorphism in the ₁-adrenoceptor was recently discovered (Gly389Arg ADRB1). We examined the association between Gly389Arg ADRB1 and obesity status in a large cohort of well-characterized individuals.

Methods: First, a large cohort of 931 Caucasian women (55.0±12.2 y) were genotyped for Gly389Arg ADRB1 and we examined the association of the Arg allele with body weight and BMI (Gly/Gly, n=54; Gly/Arg, n=360; Arg/Arg, n=517). To further examine phenotypes regulating energy balance and body fatness, we examined the contribution of the Arg allele to body composition (DEXA), fat distribution (CT scan), resting energy expenditure, energy and macronutrient intake, maximal oxygen capacity, and physical activity in a subsample of 214 women from the main cohort that had been carefully characterized (Gly/Gly, n=19; Gly/Arg, n=82; Arg/Arg, n=113).

Results: In the entire cohort (n=931), allele frequencies were 0.25 and 0.75 for the Gly and Arg alleles, respectively. In this cohort, we found that each Arg allele was associated with greater body weight of 2.91 kg (P=0.01) and BMI of 0.86 kg/m² (P=0.05). Accordingly, in the subsample of women, each Arg allele was associated with greater fat mass (3.71 kg; P=0.008). Other phenotypes were not significantly associated with the presence of the Arg allele.

Conclusions: This is the first study to investigate the relationship between the Gly389Arg ADRB1 variant and obesity. We found that the Arg allele is associated with greater body weight and BMI in Caucasian women due to a greater fat mass.

International Journal of Obesity (2002) 26, 633-639. DOI:10.1038/sj/ijo/0801971

body weight; body mass index; fat mass; energy balance; genetics