Analysis of polymorphism of the GLUT2 promoter in NIDDM patients and its functional consequence to the promoter activity

Ji Young Cha, Hyon Suk Kim, Ha Il Kim, Seung Soon Im, So Youn Kim, Jae Woo Kim, Byung Il Yeh, Yong Ho Ahn

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Abstract

Glucose transporter type 2 (GLUT2), along with glucokinase, has been implicated to participate in glucose-induced insulin secretion in pancreatic β-cells. Recently, several sequence variations in the promoter of GLUT2 have been identified in patients with non-insulin dependent diabetes mellitus (NIDDM), but the functional effects of these polymorphisms on promoter activity have not previously been studied. We compared the incidence of sequence variations in the GLUT2 promoter in 100 normal subjects and 100 NIDDM patients. Sequencing of the promoter region (-294 to +301) revealed that an A→G variant at position -44 was found in 45 of 100 NIDDM patients, but only in 23 of 100 normal subjects. In addition, -269 A→C and +103 A→G mutations were identified in a single diabetic patient. Electrophoretic mobility shift assays using double-stranded oligonucleotide containing -44A as a probe showed a clearly shifted band of DNA-protein. To examine whether the sequence variation at position -44 affects the promoter activity, we carried out in vitro transfection experiments. Site-specific mutagenesis at position -44 region from A to C, T, or G resulted in reductions of CAT activity by 52.3%, 63.8%, and 63.6%, respectively. The -269 A→C and +103 A→G mutations also decreased the promoter activity. These results suggest that polymorphisms at positions -269, -44, or +103 may affect GLUT2 gene transcription, possibly associated with reduced expression of the GLUT2 gene in NIDDM patients.

Original languageEnglish
Pages (from-to)114-122
Number of pages9
JournalAnnals of Clinical and Laboratory Science
Volume32
Issue number2
Publication statusPublished - 2002 May 8

Fingerprint

Glucose Transporter Type 2
Medical problems
Polymorphism
Type 2 Diabetes Mellitus
Genes
Glucokinase
Electrophoretic mobility
Mutagenesis
Mutation
Electrophoretic Mobility Shift Assay
Transcription
Site-Directed Mutagenesis
Genetic Promoter Regions
Oligonucleotides
Transfection
Assays
Insulin
Glucose
DNA
Incidence

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology
  • Molecular Biology
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology

Cite this

Cha, Ji Young ; Kim, Hyon Suk ; Kim, Ha Il ; Im, Seung Soon ; Kim, So Youn ; Kim, Jae Woo ; Yeh, Byung Il ; Ahn, Yong Ho. / Analysis of polymorphism of the GLUT2 promoter in NIDDM patients and its functional consequence to the promoter activity. In: Annals of Clinical and Laboratory Science. 2002 ; Vol. 32, No. 2. pp. 114-122.
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Analysis of polymorphism of the GLUT2 promoter in NIDDM patients and its functional consequence to the promoter activity. / Cha, Ji Young; Kim, Hyon Suk; Kim, Ha Il; Im, Seung Soon; Kim, So Youn; Kim, Jae Woo; Yeh, Byung Il; Ahn, Yong Ho.

In: Annals of Clinical and Laboratory Science, Vol. 32, No. 2, 08.05.2002, p. 114-122.

Research output: Contribution to journalArticle

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AU - Cha, Ji Young

AU - Kim, Hyon Suk

AU - Kim, Ha Il

AU - Im, Seung Soon

AU - Kim, So Youn

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AU - Yeh, Byung Il

AU - Ahn, Yong Ho

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