Diabetologia

, Volume 35, Issue 5, pp 486–489

Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a welsh type 2 (non-insulin-dependent) diabetic population

  • S. O'Rahilly
  • A. Krook
  • R. Morgan
  • A. Reese
  • J. S. Flier
  • D. E. Moller
Rapid Communications

DOI: 10.1007/BF02342449

Cite this article as:
O'Rahilly, S., Krook, A., Morgan, R. et al. Diabetologia (1992) 35: 486. doi:10.1007/BF02342449

Summary

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 4383 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 this 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. The genotypic frequencies (homozygous wild-type and heterzygous polymorphic (poly) sequences) were not significantly different between diabetic and control subjects (Type 2 diabetic subjects: wild-type/wild-type 40%, wild-type/poly 46%, poly/poly 14%; Control subjects: wild-type/wild-type 37%0, wild-type/poly 45 %, poly/poly 18 %;p > 0.05). In conclusion, in a British Caucasian population the examined insulin receptor tyrosine kinase domain mutations are uncommon. Also the GLUT 4 locus does not appear to be strongly associated with Type 2 diabetes.

Key words

GeneticsType 2 (non-insulin-dependent)diabetes mellitusinsulin receptorglucose transporters

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • S. O'Rahilly
    • 1
  • A. Krook
    • 1
  • R. Morgan
    • 2
  • A. Reese
    • 2
  • J. S. Flier
    • 3
  • D. E. Moller
    • 3
  1. 1.Departments of Medicine and Clinical Biochemistry, University of CambridgeAddenbrooke's HospitalCambridgeUK
  2. 2.Department of MedicineUniversity Hospital of WalesCardiffUK
  3. 3.Department of MedicineBeth Israel HospitalBostonUSA