title: Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects.
abstract: The beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations using single-strand conformation polymorphism analysis (SSCP) in 30 Japanese subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all exons and adjacent intron regions identified six SSCP polymorphisms, three of which resulted in amino acid substitutions: V101I, T110I and G519E. The V101I and G519E, substitutions represent new polymorphisms in this gene. The six polymorphisms were observed in both NIDDM and control groups and there were no significant differences in allele frequencies between groups. A portion of the insulin receptor substrate 1 gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations. Two SSCP variants that change the sequence of the protein, delta S686/687 (deletion of the codons for serine-686 and 687) and G972R, were identified in two different NIDDM subjects, both whom were also heterozygous for the V101I polymorphisms in GLUT2. The GLUT2 and IRS1 amino acid polymorphisms did not show a simple pattern of co-inheritance with NIDDM in the families of these subjects suggesting that neither polymorphism is sufficient to cause NIDDM but may increase diabetes-susceptibility through their interaction with other loci and environmental factors.
authors.affiliation: Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Makino
authors.forename: H
authors.initials: H
authors.lastname: Iwaoka
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
authors.forename: A
authors.initials: A
authors.lastname: Kanatsuka
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D051273:Glucose Transporter Type 2; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D051273:Glucose Transporter Type 2; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D009004:Monosaccharide Transport Proteins; D010750:Phosphoproteins