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Non-insulin-dependent diabetes mellitus (NIDDM) is a phenotypically and genetically heterogeneous disorder. A recent random genome mapping study has localized a locus termed NIDDM2 that maps to the region of chromosome 12 that includes MODY3, one of the three genes responsible for maturity-onset diabetes of the young, a monogenic form of NIDDM characterized by early age of onset and autosomal dominant inheritance. These findings suggest that NIDDM2 and MODY3 may represent different alleles of the same gene. MODY3 has recently been shown to be the gene encoding the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) thereby allowing us to determine whether mutations in the HNF-1 alpha gene are present in subjects with late-onset NIDDM. We screened 84 white NIDDM patients of Danish ancestry and found four nucleotide substitutions that changed the sequence of HNF-1 alpha, Ile27-->Leu, Ala98-->Val, Ser487-->Asn and Arg583-->Gln, five nucleotide substitutions that were silent and did not change the amino acid, Leu17, Gly288, Leu459 and Thr515, and five substitutions in the intron regions. The frequencies of the codon 27, 98 and 487 amino acid variants were similar in 245 unrelated NIDDM patients and 242 age-matched control subjects. The Arg583-->Gln mutation was found in 2 of 245 NIDDM patients and in none of the control subjects. Thus, genetic variation in the HNF-1 alpha gene is not a common factor contributing to NIDDM susceptibility in white subjects of Danish ancestry.

Original publication

DOI

10.1007/s001250050703

Type

Journal article

Journal

Diabetologia

Publication Date

04/1997

Volume

40

Pages

473 - 475

Addresses

Steno Diabetes Center, Copenhagen, Denmark.

Keywords

Chromosomes, Human, Pair 12, Humans, Diabetes Mellitus, Type 2, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors, Codon, DNA Primers, Chromosome Mapping, Polymerase Chain Reaction, Age of Onset, Base Sequence, Gene Frequency, Point Mutation, Polymorphism, Single-Stranded Conformational, Exons, Middle Aged, European Continental Ancestry Group, Denmark, Female, Male, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Genetic Variation