SYNERGISTIC EFFECT OF POLYMORPHISMS IN UNCOUPLING PROTEIN-1 AND BETA(3)-ADRENERGIC RECEPTOR GENES ON BASAL METABOLIC-RATE IN OBESE FINNS

The polymorphisms in the uncoupling pro tein 1 (UCP1, A to G) and beta (3)-adrenergic receptor (beta(3)-AR, Trp64Arg) genes have been suggest ed to be associated with an increased tendency to gain weight. We inve stigated the frequency of the A to G polymorphism of the UCP1 gene and its effect on basal metabolic rate (BMR) among obese Finns. We also e xamined the effects of the simultaneous occurrence of the polymorphism s in the UCP1 and beta(3)-AR genes on BMR. Altogether 170 obese subjec ts (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m(2), age 43 +/- 8 years, m ean +/- SD) participated in the study. The A to G substitution of the UCP1 gene was verified by digestion of the PCR product with BclI. The frequency of the A to G polymorphism of the UCP1 gene in obese subject s did not differ significantly from the population-based control subje cts (5 vs 1% for homozygotes (GC) and 35 vs 42 % for heterozygotes (AG ), p = 0.077, for trend). BMR adjusted for lean body mass, age and sex (adjBMR) was similar among the three UCP1 gene genotypes of obese sub jects (AA n = 90, AG n = 72 or GG n = 8). However, the subjects with t he polymorphisms in both UCP1 and beta(3)-AR genes (n = 18) had a 79 k cal/day (95 % CI 30-128) lower adjBMR than the subjects without these polymorphisms (n = 76) (1551 +/- 77 vs 1629 +/- 141 kcal/day, p = 0.00 2). Furthermore, adjBMR was 63 kcal/day (95% CI 7-118 kcal/day) lower in the subjects with both polymorphisms (n = 18) compared with the sub jects (n = 14) who had only the polymorphism in the beta(3)-AR gene (1 551 +/- 77 vs 1613 +/- 76 kcal/day, p = 0.028). The A to G polymorphis m of the UCP1 gene did not have an independent effect on BMR, but its simultaneous existence with the Trp64Arg polymorphism of the beta(3)-A R gene resulted in more lowered BMR than the Trp64Arg polymorphism of beta(3)-AR gene alone.