Mutations in the genes for hepatocyte nuclear factor (HNF)-1α,-4α,-1β, and-3β;: 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 heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODI( can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset ripe 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS - The coding regions of the known MODY genes hepatocyte 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 DNA from Pima Indians. The primary "affected" study population consisted of 46 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 then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 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 an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS - Mutations in these known MODY or MODE candidate genes are not a common cause of early-onset diabetes ill Pima Indians.