Objective: The uncoupling protein 2 (UCP2) uncouples respiration from the oxidative phosphorylation in most cell types, predominantly in white fat and skeletal muscle. Since a decreased basal metabolic rate (BMR) would increase the susceptibility to weight gain, genetic alterations in the UCP2 gene could contribute to the pathogenesis of obesity and the metabolic syndrome (MSDR).
Design and methods: To test this hypothesis, we PCR amplified the introns of the UCP2 gene and sequenced the exon/intron boundaries. This information was used to construct intronic primers and to screen obese patients with low BMR for mutations in the coding regions of the UCP2 gene, using the single-strand conformational polymorphism technique. Furthermore, we examined whether there is an association between a biallelic marker in the UCP2 gene and BMR or MSDR.
Results: The UCP2 gene is composed of six coding exons, covering 5 kb of chromosome 11q13. One polymorphism, but no mutations, were identified in the coding regions of the UCP2 gene. There were no significant differences in the allele or genotype frequencies of the Ala55Val polymorphism between 55 patients with MSDR and 46 healthy controls. No association was found between the UCP2 gene and BMR in patients with MSDR or in healthy controls.
Conclusions: Mutation screening and association studies suggest that mutations in the coding regions of the UCP2 gene do not affect BMR and do not contribute to increased susceptibility to obesity or MSDR. The results cannot, however, exclude the possibility that variants in regulatory elements of the gene could contribute to the development of obesity or MSDR.