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Studies of the Synergistic Effect of the Trp/Arg⁶⁴ Polymorphism of the ß₃-Adrenergic Receptor Gene and the -3826 AG Variant of the Uncoupling Protein-1 Gene on Features of Obesity and Insulin Resistance in a Population-Based Sample of 379 Young Danish Subjects¹

Steno Diabetes Center and Hagedorn Research Institute (S.A.U., T.H., K.B.-J., O.P.); and Center of Preventive Medicine, Glostrup University Hospital (K.B.-J.), DK-2820 Gentofte, Copenhagen, Denmark

Address all correspondence and requests for reprints to: Søren A. Urhammer, M.D., Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark.

This study examined whether the simultaneous presence of the previously identified Trp/Arg⁶⁴ polymorphism of the ß₃-adrenergic receptor (BAR) gene and the -3826 AG nucleotide variant of the uncoupling protein-1 (UCP1) gene are associated with obesity, insulin resistance, or alterations in size at birth in a Danish study population comprising 379 unrelated young Caucasian subjects. All study participants underwent an iv glucose tolerance test with addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the 2 polymorphisms by applying PCR-restriction fragment length polymorphism. The subjects were divided into 4 groups according to their BAR and UCP1 genotype: wild-type carriers (n = 184), only Trp/Arg⁶⁴ carriers (n = 29), only AG UCP1 carriers (n = 146), and carriers of both genetic variants (n = 20). There were no differences across the genotype groups with respect to body mass index, fat mass, waist to hip ratio, birth weight or length, ponderal index, or weight gain during childhood or adolescence, nor was the combined genotype related to alterations in fasting serum levels of lipids, insulin, or C peptide or the insulin sensitivity index. In conclusion, the present study failed to demonstrate an additive or synergistic effect of the Trp/Arg⁶⁴ variant of the BAR gene and the -3826 AG variant of the UCP1 gene on the development of obesity and insulin resistance among randomly recruited Danish Caucasian subjects.

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