RELATIONSHIP OF A NOVEL POLYMORPHIC MARKER NEAR THE HUMAN OBESE (OB) GENE TO FAT MASS IN HEALTHY WOMEN

The cloning of the murine obese (ob) gene and its human homologue has recently been reported, Mutations in the mouse ob gene result in hered itary obesity; however, the role of variations of OB in the regulation of bodyweight in humans has yet to be determined, The contribution of putative genetic variations in the human OB gene to total and regiona l fat mass in a normal tw in population has been analyzed through link age and association with a novel polymorphic marker, located in proxim ity to this gene, The polymorphic dinucleotide repeat, isolated from a P1 clone containing the human OB gene, was physically localized by lo ng-range restriction mapping to within 30 kilobases of the OB locus, T he marker was genotyped in a population of 47 healthy female/female di zygotic (DZ) twin pairs for which direct measures of central abdominal and whole body fat had been obtained by dual X-ray absorbtiometry. Po ssible linkage between the microsatellite marker and whole-body (p=0.0 08), but not central abdominal (p=0.09), fat deposits was indicated, N o association between fat depot phenotype and marker genotype was dete cted, These results suggest that genetic variation in or close to the human OB gene may play a role in the size of body fat stores in health y women.