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Expert
Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 8; Issue 4; 7 February 2006 Abstract
PDF
The 5' flanks of the human and mouse GLUT1 genes
Charles W. Heilig, Frank C. Brosius III and Carol Cunningham
Figure 2. The 5' flanks
of the human and mouse GLUT1 genes. (a) Human GLUT1 gene.
Single nucleotide polymorphism (SNP) sites in the 5' end of the human GLUT1
gene that have been analysed for an association with diabetic nephropathy are
shown. The AA genotype at the enhancer 2, SNP1 (Enh2SNP1) site (in intron 2)
has been reported to be associated with increased risk for diabetic nephropathy
in type 1 diabetics (Ref. 76). This SNP is reported to be
located in a putative E-box motif (CCCATG), a potentially glucose-responsive
site where USF transcription factors (upstream stimulating factors) may bind.
A more recent, preliminary report has demonstrated that the AA GLUT1
genotype is also associated with increased risk for nephropathy in type 2 diabetics,
and even in nondiabetics (Ref. 77). The T allele at the A–2841T
SNP in the human GLUT1 promoter was recently shown to be tightly associated
with increased risk for the nephropathy in type 1 diabetic subjects (Ref. 79).
The polymorphic Xba1 diabetic nephropathy susceptibility site is shown in intron
2 and is described in the text. The human GLUT1 map (not drawn to scale)
was modified from Ref. 76 (Copyright © 2002 American
Diabetes Association), with permission from the American Diabetes Association
and from Andrzej Krolewski. (b) Mouse GLUT1 gene. The mouse GLUT1
gene is known to be responsive to glucose. The enhancer 1 and 2 sites each contain
two putative E-boxes, plus either two nonconsensus TPA-responsive elements (TREs)
(enhancer 1), or two consensus TREs (enhancer 2). All of these sites are potential
glucose-response sites in the gene. By contrast, the mouse GLUT1 promoter has
two putative E-boxes, but no typical TREs. The mouse map (not drawn to scale)
was modified from Ref. 97 (Copyright © 1992 The American
Society for Biochemistry and Molecular Biology, Inc.), with permission from
The American Society for Biochemistry and Molecular Biology and from Yousuke
Ebina.
| References cited
in Figure 2
76 Ng, D.P. et al. (2002) Minor effect of GLUT1 polymorphisms on susceptibility to diabetic nephropathy in type 1 diabetes. Diabetes 51, 2264-2269, PubMed 77 Hsu, C. et al. (2004) Genetic variation of glucose transporter 1 (GLUT1) and nephropathy in the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes 53 (Suppl 2), 1-80 79 Tarnow, L. et al. (2001) Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients. Nephrol Dial Transplant 16, 1653-1656, PubMed 97 Murakami, T. et al. (1992) Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. J Biol Chem 267, 9300-9306, PubMed |
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