Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians

The human proto-oncogene PBX1 codes for a homeodomain containing protein th at modulates expression of several genes, including those contributing to r egulation of insulin action and glucose metabolism. PBX1 is located on chro mosome 1q22, a region linked with type 2 diabetes in Pima Indians. Caucasia ns. and an Old Order Amish population. We have investigated the PBX1 genomi c sequence to identify polymorphisms that may contribute to diabetes suscep tibility in the Pimas. PBX1 is composed of nine exons spanning approx. 117 kb and is located within 300 kb of microsatellite D1S1677, which marks the peak of linkage to diabetes susceptibility in the Pima Indians. We detected 16 single nucleotide polymorphisms in PBX1 including one causing a glycine to serine substitution at residue 21. Comparison of the frequencies of the polymorphisms between affected and unaffected Pima Indians did not detect any significant differences, indicating that mutations in PBX1 do not expla in the linkage of Iq with type 2 diabetes in this population. The genomic s tructure of PBX1 provides a basis for similar systematic examinations of th is candidate locus in other populations in relation to both type 2 diabetes and other metabolic disorders. (C) 2001 Elsevier Science B.V. All rights r eserved.