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

J Hum Genet. 1998;43(2):107-10. doi: 10.1007/s100380050049.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Asian People / genetics*
  • Child
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Genes, Dominant
  • Health Surveys
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Japan / epidemiology
  • Nuclear Proteins*
  • Point Mutation
  • Prevalence
  • Transcription Factors / genetics*
  • White People / genetics


  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Insulin
  • Nuclear Proteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • DNA