Further evidence for a susceptibility locus for type 2 diabetes on chromosome 20q13.1-q13.2

We previonsly reported suggestive linkage between type 2 diabetes and marke rs in a region on chromosome 20q using data from a collection of 29 Caucasi an families in which type 2 diabetes with middle-age-onset was segregated a s an autosomal-dominant disorder. To map more precisely the susceptibility locus (or loci) within this broad region, we increased the family collectio n and genotyped all families for additional markers, both within the critic al region and spaced over the rest of chromosome 20. Altogether 526 individ uals (including 241 with diabetes) from the total collection of 43 families were included in the study. All individuals mere genotyped for 23 highly p olymorphic markers. Positive evidence for Linkage was found for a 10-cM reg ion on the long arm of chromosome 20q13.1-q13.2 between markers D20S119 and D20S428. The strongest evidence in two-point as well as multipoint linkage analysis (P = 1.8 x 10(-5)) occurred at the position corresponding to mark er D20S196. The individuals with diabetes in the seven most strongly linked families had high serum insulin levels during fasting and 2-h post-glucose load periods. me did not find any evidence for linkage between type 2 diab etes and any other region on chromosome 20. In conclusion, our larger and m ore comprehensive study showed very strong evidence for a susceptibility ge ne for insulin-resistant type 2 diabetes located on the long arm of chromos ome 20 around marker D20S196.