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Additive Effects of the Mutations in the ß₃-Adrenergic Receptor and Uncoupling Protein-1 Genes on Weight Loss and Weight Maintenance in Finnish Women¹

The UKK Institute for Health Promotion and Research (M.F., K.K.-H., A.N.), Tampere; and the Departments of Clinical Nutrition (R.V., V.H., M.U.) and Medicine (M.L.), University of Kuopio, Kuopio, Finland

Address all correspondence and requests for reprints to: Dr. Mikael Fogelholm, The UKK Institute, POB 30, 33501 Tampere, Finland. E-mail: mikael.fogelholm{at}helsinki.fi

This study examined whether the Trp⁶⁴Arg mutation in the ß₃-adrenergic receptor (ß₃AR) and the AG 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/m²), 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 ß₃AR and UCP-1 genotype: no mutation (control; n = 37), only Trp⁶⁴Arg mutation in the ß₃AR gene (n = 12), only AG 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 Trp⁶⁴Arg mutation in the ß₃AR and the AG mutation in the UCP-1 genes may be associated with faster weight gain after a VLCD.

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