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 raisedthe possibility that it may be involved in regulation of energy balance. Toexplore this concept we have investigated potential linkage relationshipsbetween three microsatellite markers which encompass the UCP2 gene locationon 11q13 with resting metabolic rate (RMR), body mass index, percentagebody fat (%FAT) and fat mass (FM) in 640 individuals from 155 pedigreesfrom the Quebec Family Study. Using a linkage analysis strategy based onsibling, avuncular, grandparental and cousin pairs, strong evidence oflinkage was found between the marker D11S911 (P = 0.000002) and RMR, withmore moderate evidence for D11S916 (P = 0.006) and D11S1321 (P = 0.02).Suggestive evidence of linkage was also observed between D11S1321 and %FAT(P = 0.04) and FM (P = 0.02). It is concluded that the three markersencompassing the UCP2 locus and spanning a 5 cM region on 11q13 are linkedto resting energy expenditure in adult humans. The evidence is strongenough to warrant a search for DNA sequence variation in the gene itself.