Additive effects of the mutations in the β3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women

This study examined whether the Trp(64)Arg mutation in the beta(3)-adrenergic receptor (beta(3)AR) and the A-->G mutation in the uncoupling protein-1. (UCP-1) genes have associations with weight loss and subsequent weight maintenance. Seventy-seven obese (body mass index range, 29-46 kg/m(2)), clinically healthy, premenopausal women were studied. A 12-wk weight reduction by very low calorie diet (VLCD) was followed by a 40-wk weight maintenance phase. The subjects were divided into four groups according to their beta(3)AR and UCP-1 genotype: no mutation (control; n = 37), only Trp(64)Arg mutation in the beta(3)AR gene (n = 12), only A-->G mutation in the UCP-1 gene (n = 23), and both mutations (n = 5). Subjects with both mutations had a lower weight reduction during VLCD than the controls [-10.5 +/- 0.6 (+/- SEM) vs. -14.0 +/- 0.5 kg; P = 0.051, by ANOVA]. During the maintenance phase, weight in subjects with both mutations increased by 5.8 +/- 1.5 kg, but remained unchanged in the controls (- 0.5 +/- 0.8 kg; P = 0.041). The changes in weight in subjects with only one of the mutation were close to the results in the controls. Resting energy expenditure, adjusted for fat mass, fat-free mass, and maximal aerobic power, did not change differently between the groups throughout the study. The results suggest that a combination of the Trp(64)Arg mutation in the beta(3)AR and the A-->G mutation in the UCP-1 genes may be associated with faster weight gain after a VLCD.