| The Akimel O'Odham, the people of the Gila River Pima Indian Community of central Arizona, have the highest known risk for Type 2 Diabetes (T2D). The National Institute of Digestive, Diabetes, and Kidney Disease (NIDDK), of the National Institutes of Health (NIH) has been studying T2D in this population since 1964. One arm of this study seeks genetic factors which contribute to etiology of the disease. This report encompasses study findings of physiological and positional candidate genes for T2D in this population. The physiological candidate genes, SUR1 and Kir6.2, expressed in beta cells play a critical role in insulin secretion. Futhermore, they have been shown rich in genetic variation. This report documents the polymorphisms found in Pimas. Linkage studies revealed linkage between loci on chromosome 4 and chromosome 11q and disease. Previous work in this laboratory showed functional consequences associated with a missense mutation in intestinal fatty acid binding protein (FABP2). Included here are results of a functionality study of variation in the FABP2 5'-UTR region. A topical review presents the current understanding of the role of this protein. The final section contains results from a portion of the chromosome 11q 50-kb fine-mapping project undertaken by this laboratory. This project followed the earlier report that linkage studies showed association between BMI and diabetes to loci on chromosome 11q. In addition to fine-mapping, the laboratory sequenced genes in the region. The results of sequencing DPAGT1, one of the positional candidate genes indicated by the linkage study, are presented. |
