Evidence for linkage of regions on chromosomes 6 and 11 to plasma glucose concentrations in Mexican Americans

The generic factors involved in type II diabetes are still unknown. To address this problem, we are creating a 10 to 15 cM genetic map on 444 individuals from 32 Mexican American families ascertained on a type II diabetic proband. Using highly polymorphic microsatellite markers and a multipoint variance components method, we found evidence for linkage of plasma glucose concentration 2 hr after oral glucose administration to two regions on chromosome II: beta-hemoglobin (HBB) and markers D11S899/D11S/324 near the sulfonylurea receptor (SUR) gene. lod scores at these two loci were 2.77 acid 3.37, respectively. The SUR gene region accounted for 44.7% of the phenotypic variance. Evidence for linkage to fasting glucose concentration was also observed for two loci on chromosome 6, one of which is identical to a proposed susceptibility locus for type I diabetes (D6S290). When diabetics were excluded from the analyses, all lod scores became zero, suggesting that the observed linkages were with the trait diabetes rather than with normal variation in glucose levels. Results were similar whether ail diabetics were included in the analyses or only those who were not under treatment with oral antidiabetic agents or insulin.