AVAILABILITY OF TYPE-II DIABETIC FAMILIES FOR DETECTION OF DIABETES SUSCEPTIBILITY GENES

Type II diabetes is a familial disorder, as evidenced by the increased prevalence in monozygotic cotwins and first-degree relatives of affec ted subjects; however, its genetic etiology is largely unknown. Well-c haracterized pedigrees are an essential resource for the study of susc eptibility genes for type II diabetes. This study describes a 5-yr sea rch for type II diabetic families in Oxfordshire, U.K. We interviewed 950 type II diabetic subjects concerning the availability of first-deg ree relatives; 127 Caucasian families ascertained through a proband wi th type II diabetes were studied, and 589 first-degree relatives were characterized. Three large pedigrees with maturity-onset diabetes of t he young, and 8 multiplex multigenerational type II diabetic pedigrees were identified. We identified 12 sib-pairs in which both siblings ha d type II diabetes; however, only 7 sib-pairs had both parents alive, and 2 of these had both parents affected. If one also considers one si b having diabetes and one sib having glucose intolerance as being an a ffected sib-pair, we identified 30 sib-pairs of which 7 had both paren ts affected and probably had bilineal inheritance. We identified 76 co mplete nuclear families with both parents and offspring available for study, but only 6 were of optimal structure for linkage analysis. In c onclusion, multiplex pedigrees and type II diabetic sib-pairs with liv ing parents are uncommon, and their ascertainment requires a substanti al investment of resources. Large-scale collaborative multicenter init iatives would be needed to collect a large resource of family material for the study of susceptibility genes for type II diabetes.