Association of hGrb10 Genetic Variations With Type 2 Diabetes in Caucasian Subjects

The genes contributing to type 2 diabetes are mostly unknown (1). Grb10 is an adapter protein that, in target tissues (2,3), interacts with the insulin receptor (3–9), thus affecting downstream signaling (10–12) and insulin action (2,7,10–16). We tested the hypothesis that variants in the Grb10 gene modulate the risk for type 2 diabetes, one of the most frequent outcomes of insulin resistance. Resequencing of coding and immediately flanking sequences of hGrb10 (17,18) identified six single nucleotide polymorphisms (SNPs), five of which had a minor allele frequency >5%. Based on their physical location and their mutual linkage disequilibrium, these five SNPs (i.e., rs1800504, rs2715128, rs2072235, rs4947710, and …