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

Abstract

We previously reported suggestive linkage between type 2 diabetes and markers in a region on chromosome 20q using data from a collection of 29 Caucasian families in which type 2 diabetes with middle-age-onset was segregated as an autosomal-dominant disorder. To map more precisely the susceptibility locus (or loci) within this broad region, we increased the family collection and genotyped all families for additional markers, both within the critical region and spaced over the rest of chromosome 20. Altogether 526 individuals (including 241 with diabetes) from the total collection of 43 families were included in the study. All individuals were genotyped for 23 highly polymorphic markers. Positive evidence for linkage was found for a 10-cM region 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 marker 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. We did not find any evidence for linkage between type 2 diabetes and any other region on chromosome 20. In conclusion, our larger and more comprehensive study showed very strong evidence for a susceptibility gene for insulin-resistant type 2 diabetes located on the long arm of chromosome 20 around marker D20S196.