title: Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population.
abstract: We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4(383) variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of the mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: A
authors.initials: A
authors.lastname: Krook
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Rees
authors.forename: J S
authors.initials: JS
authors.lastname: Flier
authors.forename: D E
authors.initials: DE
authors.lastname: Moller
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000235:genetics*; D012016:Reference Values; D015183:Restriction Mapping; D014852:Wales
chemical_list: D003062:Codon; D009004:Monosaccharide Transport Proteins; D009838:Oligodeoxyribonucleotides; D011972:Receptor, Insulin