title: Mutations in the hepatocyte nuclear factor-1 alpha gene (MODY3) are not a major cause of early-onset non-insulin-dependent (type 2) diabetes mellitus in Japanese.
abstract: Maturity-onset diabetes of the young (MODY3), a monogenic subtype of non-insulin-dependent diabetes mellitus (NIDDM) with an early age of onset, is characterized by a primary defect in insulin secretion. Recently, it has been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) cause MODY3. Since NIDDM in Japanese is characterized by insulin secretory defects due to primary beta-cell dysfunction, we screened 60 Japanese nonobese subjects with early-onset NIDDM for mutations in this gene, 45 of whom had a first-degree relative with NIDDM. Direct sequencing of the ten exons and flanking introns of the gene in these subjects identified eight nucleotide substitutions including two amino acid changes, Ile-27-Leu and Ser-487-Asn, the frequencies of which were not significantly different in subjects with early-onset NIDDM and nondiabetic subjects. These results suggest that mutations in the HNF-1 alpha gene are not a major cause of early-onset NIDDM in Japanese.
authors.affiliation: Department of Cell Biology, Gunma University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishigori
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Kohama
authors.forename: T
authors.initials: T
authors.lastname: Utsugi
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: J
authors.initials: J
authors.lastname: Takeda
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D002648:Child; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005799:Genes, Dominant; D006306:Health Surveys; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007564:Japan / Q000453:epidemiology; D009687:Nuclear Proteins; D017354:Point Mutation; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007328:Insulin; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA