LINKAGE BETWEEN MARKERS IN THE VICINITY OF THE UNCOUPLING PROTEIN-2 GENE AND RESTING METABOLIC-RATE IN HUMANS

The recent cloning of a gene that codes for a novel uncoupling protein , UCP2, which is expressed in a wide range of adult human tissues, has raised the possibility that it may be involved in regulation of energ y balance. To explore this concept we have investigated potential link age relationships between three microsatellite markers which encompass the UCP2 gene location on 11q13 with resting metabolic rate (RMR), bo dy mass index, percentage body fat (%FAT) and fat mass (FM) in 640 ind ividuals from 155 pedigrees from the Quebec Family Study. Using a link age analysis strategy based on sibling, avuncular, grandparental and c ousin pairs, strong evidence of linkage was found between the marker D 11S911 (P = 0.000002) and RMR, with more moderate evidence for D11S916 (P = 0.006) and D11S1321 (P = 0.02), Suggestive evidence of linkage w as also observed between D11S1321 and %FAT (P = 0.04) and FM (P = 0.02 ), It is concluded that the three markers encompassing the UCP2 locus and spanning a 5 cM region on 11q13 are linked to resting energy expen diture in adult humans. The evidence is strong enough to warrant a sea rch for DNA sequence variation in the gene itself.