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

Authors
 Jiyoung Cha  ;  Hyonsuk Kim  ;  Hail Kim  ;  Seungsoon Im  ;  Soyoun Kim  ;  Jaewoo Kim  ;  Byungil Yeh  ;  Yongho Ahn 
Citation
 Annals of Clinical and Laboratory Science, Vol.32(2) : 114-122, 2002 
Journal Title
 Annals of Clinical and Laboratory Science 
ISSN
 0091-7370 
Issue Date
2002
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.
Full Text
http://www.annclinlabsci.org/content/32/2/114
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
김재우(Kim, Jae Woo) ORCID logo https://orcid.org/0000-0001-5456-9495
김하일(Kim, Ha Il)
안용호(Ahn, Yong Ho) ORCID logo https://orcid.org/0000-0002-4133-0757
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144686
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