Previous observations of variation associated with the acute insulin response suggested that his phenotype was controlled by on or more genes. Glucokinase, which has been linked to the MODY form of diabetes, has also been proposed as a intracellular glucose sensor appeared to be a likely candidate gene. Similarly, glut-2 the major glucose transporter of the pancreas could also be responsible for the variation observed in the acute insulin response. Polymorphisms at both of these genes have been examined for an association or linkage with the acute insulin response, and analysis of 117 sibpairs suggests there is linkage between this region on chromosome 3 and the acute insulin response. A structural analysis of the coding regions for the gene encoding glut-2 revealed a single transition which predicts an amino acid substitution at position 110 of Glut2. It is currently unknown how the mutation effects glucose sensing in the Beta-cell. Additional short tandem repeat polymorphisms (STRPs) have been genotyped in the region of GLUT2. Specifically, an additional STRP within GLUT2, with higher heterozygosity, was genotyped in 1000 Pima Indians. Sibpair linkage analysis did not support our earlier observation of week linkage to the acute insulin response. While linkage to the acute insulin response was not supported, linkage (p-0.02) to maximum body mass index was observed. Two other markers flanking Glut2 also showed linkage to this trait. The marker D3S1237, proximal to Glut2, showed the tightest linkage to maximum body mass index (p=0.0006). Project is now part of Genetic and Physical Mapping of Phenotypic Traits in Pima Indians (Z01 DK 69057, and terminated as independent project.
