Single-strand conformation polymorphism analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young

M. Baroni, F. Sentinelli, O. Massa, S. Romeo, C. Colombo, U. Di Mario, F. Barbetti

Research output: Contribution to journalArticle

Abstract

Maturity-onset diabetes of the young (MODY), an autosomal dominant, early-onset form of type-2 diabetes, is caused by mutations in five different genes all leading to defect(s) in the pancreatic β cell. However, some patients with this form of diabetes do not bear a mutation in any of the known (MODY1 - MODY5) loci, a notion prompting the search for new MODY genes. Clinical and genetic data point toward a defect in β cell function in the majority of patients with MODY, and partners of the glucose-sensing device are reasonable functional candidates. The high-capacity glucose transporter GLUT2 has the ideal kinetic features for performing this task. However, complete GLUT2 deficiency in humans leads to hepato-renal glycogenosis (Fanconi-Bickel syndrome), and heterozygous GLUT2 mutations apparently behave in a recessive manner. Furthermore, in the human β cell GLUT1 mRNA is predominant when compared to GLUT2 and glucose influx appears to be largely mediated by this low-Km transporter. Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1α (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. We found three already described silent mutations and a new single base deletion in position -173 of the 5′ regulatory region. The -173delA variant, which was detected in the heterozygous or homozygous state in 30.8% of MODY patients examined and is located in a Nuclear Factor Y binding sequence, is not associated with hyperglycemia in affected relatives of MODY probands. In conclusion, it appears from these results that the glucose transporter gene GLUT1 is unlikely to play a major role in the etiology of MODY diabetes.

Original languageEnglish
Pages (from-to)270-274
Number of pages5
JournalJournal of Molecular Medicine
Volume79
Issue number5-6
DOIs
Publication statusPublished - 2001

Keywords

  • DNA mutations
  • GLUT1 gene
  • GLUT2 gene
  • Maturity-onset diabetes of the young (MODY)
  • Single-strand conformation polymorphism (SSCP)

ASJC Scopus subject areas

  • Medicine(all)

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