title: Sequence variations of the pancreatic islet/liver glucose transporter (GLUT2) gene in Japanese subjects with noninsulin dependent diabetes mellitus.
abstract: To assess the genetic susceptibility to noninsulin-dependent diabetes mellitus (NIDDM) in Japanese subjects, we investigated the role of GLUT2 gene defects in patients with NIDDM. When the allelic frequency of a simple tandem repeat polymorphism in the GLUT2 gene was compared, the allele with 155 base pairs was more common in NIDDM patients (n = 99) than in controls (n = 89; 5.1% vs. 0.6%; P = 0.0118, by Fisher's exact test), whereas this was not significant after the correction for multiple comparisons. To directly identify mutations, we then analyzed each of 11 exons by the polymerase chain reaction-single strand conformation polymorphism analysis in 60 NIDDM patients. We found 2 missense mutations in exon 3: CCC-->CTC (Pro68-->Leu) in 1 patient and ACT-->ATT (Thr110-->Ile) in 3 patients, all in the heterozygous state. These mutations were not found in 60 control subjects. To evaluate the significance of the Pro68-->Leu mutation, the family members of the proband were studied. The mutation did not appear to be associated with the disease or other clinical parameters including change in immunoreactive insulin/change in plasma glucose or oral glucose load. The other mutation (Thr110-->Ile) is known to be functionally insignificant. We identified 4 additional nucleotide changes, all of which appeared to be silent. We concluded that the mutations in the GLUT2 gene were not major determinants of genetic susceptibility to NIDDM in Japanese.
authors.affiliation: Third Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsubara
authors.forename: Y
authors.initials: Y
authors.lastname: Tanizawa
authors.forename: A
authors.initials: A
authors.lastname: Matsutani
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: K
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005796:Genes; D014644:Genetic Variation; D051273:Glucose Transporter Type 2; D006801:Humans; D007438:Introns; D007515:Islets of Langerhans / Q000378:metabolism*; D007564:Japan; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins