LINKAGE OF GENETIC-MARKERS ON HUMAN-CHROMOSOME-20 AND HUMAN-CHROMOSOME-12 TO NIDDM IN CAUCASIAN SIB PAIRS WITH A HISTORY OF DIABETIC NEPHROPATHY

The potential contribution of maturity-onset diabetes of the young (MO DY) genes to NIDDM susceptibility in African-American and Caucasian NI DDM-affected sibling pairs with a history of adult-onset diabetic neph ropathy has been evaluated. Evidence for linkage to NIDDM was found wi th polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. Nonparametric analysis of chromosome 20 inheritance data collected with the MODY1-li nked marker D20S197 provides evidence for linkage to NIDDM with a P va lue of 0.005 in Caucasian sib pairs using affected sibpair (ASP) analy ses. Nonparametric analysis of chromosome 12 inheritance data collecte d with the MODY3-linked markers D12S349 and D12S86 provides evidence f or linkage to NIDDM with P values of 0.04 and 0.006, respectively, in Caucasian sib pairs using similar analyses. No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was ob served. In addition, no evidence for linkage to MODY2 (glucokinase-ass ociated MODY) was observed with either study population, Results of mu ltipoint maximum logarithm of odds (LOD) score analysis mere consisten t with the ASP results. A maximum LOD score of 1.48 was calculated for Linkage to MODY1-linked loci and 1.45 to MODY3-linked loci in Caucasi an sib pairs. Tabulation of allele sharing in affected sib pairs with D20S197 and D12S349 suggests that affected sibling pairs may inherit s usceptibility genes simultaneously from chromosome 20 and chromosome 1 2. The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes.