title: Glucokinase gene variants in subjects with late-onset NIDDM and impaired glucose tolerance.
abstract: OBJECTIVE
  To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT).
  
  
  METHODS
  The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for > 8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis.
  
  
  RESULTS
  A silent third-base substitution (TAC: >TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C-->G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G-->A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C-->T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects.
  
  
  CONCLUSIONS
  These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
authors.affiliation: Department of Genetics, University of Washington, Seattle, USA.
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: M
authors.initials: M
authors.lastname: Malkki
authors.forename: P
authors.initials: P
authors.lastname: Kekäläinen
authors.forename: J
authors.initials: J
authors.lastname: Kuusisto
authors.forename: L
authors.initials: L
authors.lastname: Mykkänen
authors.forename: S S
authors.initials: SS
authors.lastname: Deeb
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005941:Glucokinase / Q000235:genetics*; D018149:Glucose Intolerance / Q000201:enzymology / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007438:Introns; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011401:Promoter Regions, Genetic
chemical_list: D007328:Insulin; D005941:Glucokinase