Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity

Summary Uncoupling proteins (UCPs) are mitochondrial transporters that uncouple the cellular respiration releasing stored energy as heat. Recently a third member of the UCP family was identified. Human UCP3 is different from UCP1 and UCP2 by its high and preferential expression in skeletal muscle and consequently the UCP3 gene is an attractive candidate gene for obesity. In this study we have determined the intron/exon organization of the coding region of the UCP3 gene and performed single strand conformation polymorphism (SSCP) analysis and direct sequencing of variants of the gene in 60 Caucasian subjects with juvenile-onset obesity. We detected 4 nucleotide substitutions in the intron regions and 2 silent amino acid variants. During the identification of the intron/exon structure of the gene in a normal healthy male subject with a BMI of 23.5 kg/m², a nucleotide substitution replacing a glycine with a serine was identified at codon 84. This variant was neither found among 156 subjects with juvenile-onset obesity nor among 205 control subjects. In a population based sample of 380 young healthy subjects the Gly/Ser84 variant was found in one female subject with a BMI of 25.5 kg/m² and a fat mass of 23.7 kg. We conclude it is unlikely that variants in the coding region of the UCP3 gene contribute to the pathogenesis of juvenile-onset obesity among Danish Caucasians. [Diabetologia (1998) 41: 241–244] Received: 8 October 1997 and in revised form: 30 October 1997