Mutations in the genes for hepatocyte nuclear factor (HNF)-1 alpha,-4 alpha,-1 beta, and-3 beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in pima Indians

OBJECTIVE - Maturity-onset diabetes of the young (MODY) is a genetically he terogeneous subtype of type 2 diabetes characterized by an early age at ons et and autosomal dominant inheritance. MODI( can result from heterozygous m utations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contr ibute to the development of early-onset ripe 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS - The coding regions of the known MODY genes he patocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha, HNF-1 beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF- 3 beta and the dimerization cofactor of HNF-1, were sequenced in genomic DN A from Pima Indians. The primary "affected" study population consisted of 4 6 Pima Indians whose age at onset of type 2 diabetes was less than or equal to 20 years. DNA sequence variants identified in the affected group were t hen analyzed in a group of 80 "unaffected" Pima Indians who were at least 4 0 years old and had normal glucose tolerance. RESULTS - A total of Il polymorphisms were detected in these genes. However , none of the polymorphisms differed in frequency among Pima Indians with a n early age at onset of diabetes compared with older Pima Indians with norm al glucose tolerance. CONCLUSIONS - Mutations in these known MODY or MODE candidate genes are not a common cause of early-onset diabetes ill Pima Indians.