DO NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM) AND INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) SHARE GENETIC SUSCEPTIBILITY LOCI - AN ANALYSIS OF PUTATIVE IDDM SUSCEPTIBILITY REGIONS IN FAMILIAL NIDDM

Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as gen etically and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet many of the recently suggested IDDM susceptibilit y loci are likely to increase the risk of diabetes through nonautoimmu ne mechanisms. To test the hypothesis that the IDDM susceptibility loc i include important NIDDM susceptibility loci, we tested the linkage o f 14 putative susceptibility regions with NIDDM among families and sib ling pairs of Northern European descent. Ail regions were tested with highly informative microsatellite (simple tandem repeat) polymorphisms in up to 166 affected individuals from 42 families using both paramet ric and nonparametric methods (149 pairs for sibling pair analyses). W e found no evidence for linkage to the majority of loci, including loc i that appeared to be linked to IDDM in more than one study, We report some evidence for shared susceptibility for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus affected pedigree mem ber (APM) analysis of markers near D1S191 suggested linkage at P value .0001, This region has not yet been confirmed as an IDDM locus, and o ur analyses could represent a false-positive result. The role of these three regions will only be clarified by testing in additional familie s, In combination with other investigations in our laboratory for chro mosome 11 susceptibility regions, our data generally do not provide co nvincing evidence that IDDM and NIDDM share common genetic factors amo ng families of Northern European descent with ascertainment of two or more NIDDM siblings. Copyright (C) 1997 by W.B. Saunders Company