Studies of genetic variability of the glucose transporter 2 promoter in patients with type 2 diabetes mellitus

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  • A M Møller
  • N M Jensen
  • J Pildal
  • Drivsholm, Thomas
  • K Borch-Johnsen
  • S A Urhammer
  • T Hansen
  • O Pedersen
This study was performed to test the hypothesis that genetic variation in the promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter region of the GLUT2 gene were examined by combined single-strand conformational polymorphism and heteroduplex analysis followed by direct sequencing of identified variants on genomic DNA from 96 randomly recruited Danish type 2 diabetic patients. We identified 4 nucleotide variants, -447g-->a, -149c-->a, -122t-->c, and -44g-->a. None of the variants were positioned in known or presumed transcription factor binding sites, TATA-box, or transcriptional start site. Association studies of the -149c-->a, -122t-->c, and -44g-->a variants revealed that the variants were as prevalent in 320 type 2 diabetic patients [11.0% (95% confidence interval, 8.4-13.6), 9.8% (7.4-12.2), and 29.0% (24.4-33.6), respectively] as in 241 age-matched glucose-tolerant subjects [13.1% (9.8-16.4), 11.2% (8.3-14.1), and 33.4% (28.8-38.0), respectively]. The -447g-->a mutation was only identified in a single diabetic patient and did not show cosegregation with diabetes in the family of the proband. The three common variants showed in a primary genotype-phenotype study comprising 241 glucose-tolerant middle-aged subjects association to increased plasma glucose levels during an oral glucose tolerance test. However, this result could not be replicated in a second sample of 298 60-yr-old glucose-tolerant subjects. In conclusion, we found no evidence supporting the hypothesis that genetic variability in the minimal promoter of the GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish population.
Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
Pages (from-to)2181-6
Number of pages6
Publication statusPublished - 1 May 2001

    Research areas

  • Adult, Aged, Denmark, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Genetic Variation, Glucose Tolerance Test, Glucose Transporter Type 2, Humans, Male, Middle Aged, Monosaccharide Transport Proteins, Promoter Regions, Genetic

ID: 33030840