| KAŇKOVÁ, Kateřina, Petr BENEŠ and Šárka KUCHTÍČKOVÁ. Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy. Experimental and Clinical Endocrinology & Diabetes. Germany: Thieme, 2010, vol. 118, No 2, p. 93-5, 3 pp. ISSN 0947-7349. |
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@article{845468,
author = {Kaňková, Kateřina and Beneš, Petr and Kuchtíčková, Šárka},
article_location = {Germany},
article_number = {2},
keywords = {RAGE; hyperglycemia; transcriptional activity; haplotype; reporter assay},
language = {eng},
issn = {0947-7349},
journal = {Experimental and Clinical Endocrinology & Diabetes},
title = {Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy},
volume = {118},
year = {2010}
}
TY - JOUR
ID - 845468
AU - Kaňková, Kateřina - Beneš, Petr - Kuchtíčková, Šárka
PY - 2010
TI - Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy
JF - Experimental and Clinical Endocrinology & Diabetes
VL - 118
IS - 2
SP - 93-5
EP - 93-5
PB - Thieme
SN - 09477349
KW - RAGE
KW - hyperglycemia
KW - transcriptional activity
KW - haplotype
KW - reporter assay
N2 - The Receptor for Advanced Glycation End-products (RAGE) belongs to the family of pattern-recognition receptors and is significantly involved in the molecular mechanisms mediating pro-inflammatory action of hyperglycemia in diabetes. The aim of the current study was to elucidate the possible functional impact of the genetic variability in the AGER gene constituting previously identified risk haplotype for diabetic nephropathy (-429C/-374T/2184G) by testing the haplotype-specific effect on the AGER gene transcriptional activity in vitro. Promotor and intron 8 constructs carrying respective substitutions were amplified and cloned into pGL3-Basic reporter vector and subsequently used for transfection of HEK293 cells. Following 48hrs incubation in either normo- (5 mM/L) or hyperglycemic (25 mM/L) culture medium luciferase activity was measured to assess transcriptional efficiency. Risk haplotype was associated with the highest transcriptional activity in hyperglycemia and greatest relative increase of activity between normo- and hyperglycemia conditions (approx. 3-times). We conclude that ascertained functional differences in the regulatory regions of the AGER gene might have significant consequences for the development of hyperglycemia-related pathology in diabetics.
ER -
KAŇKOVÁ, Kateřina, Petr BENEŠ and Šárka KUCHTÍČKOVÁ. Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy. \textit{Experimental and Clinical Endocrinology \&{} Diabetes}. Germany: Thieme, 2010, vol.~118, No~2, p.~93-5, 3 pp. ISSN~0947-7349.
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