VARIATIONS IN THE VITAMIN-D-BINDING PROTEIN (GC LOCUS) ARE ASSOCIATEDWITH ORAL GLUCOSE-TOLERANCE IN NONDIABETIC PIMA-INDIANS

Electrophoretic variants of the vitamin D-binding protein (DBP) have b een associated with type 2 diabetes as well as with metabolic characte ristics that predispose to type 2 diabetes in several populations. The Ge gene that encodes DBP maps to chromosome 4q12, a region that has r ecently been found to be potentially linked to plasma glucose and insu lin concentrations in Pima Indians. Therefore, the gene that encodes D BP was analyzed as a candidate gene for our linkage findings in the Pi ma Indians. Sequence analysis of the coding exons identified two previ ously described missense polymorphisms at codons 416 and 420, which ar e the genetic basis for the three common electrophoretic variants of D BP (Gc1f, Gc1s, and Gc2). These variants in DBP were associated with d ifferences in oral glucose tolerance in nondiabetic Pima Indians.