title: Amino acid substitutions in hexokinase II among patients with NIDDM.
abstract: Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of variants in the coding region of the HKII gene in patients with NIDDM. Initial screening included a population-based sample of 40 Finnish patients with typical NIDDM, and subsequent screening included an additional 72 patients with NIDDM. By applying single-strand conformation polymorphism analysis and direct sequencing, the following amino acid substitutions were found among the 112 NIDDM patients: Ala314Val in one patient (0.9%), Arg353Cys in three patients (2.7%), and Arg775Gln substitution in three patients (2.7%). We also screened 97 subjects with completely normal glucose tolerance and a negative family history of diabetes for these mutations. The Ala314Val and the Arg353Cys substitutions were not found in control subjects, but the Arg775Gln substitution was found in two (2.1%) control subjects. None of these mutations were located close to the glucose- and ATP-binding sites of HKII. We conclude that mutations of the HKII gene are not a major etiological factor for NIDDM in the Finnish population.
authors.affiliation: Department of Genetics, University of Washington, Seattle.
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: M
authors.initials: M
authors.lastname: Malkki
authors.forename: S S
authors.initials: SS
authors.lastname: Deeb
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005387:Finland; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006593:Hexokinase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D015183:Restriction Mapping
chemical_list: D001786:Blood Glucose; D003062:Codon; D017931:DNA Primers; D007527:Isoenzymes; D006593:Hexokinase