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@article{1092044,
author = {Tanhäuserová, Veronika and Kuricová, Katarína and Pácal, Lukáš and Bartáková, Vendula and Řehořová, Jitka and Svojanovský, Jan and Olšovský, Jindřich and Bělobrádková, Jana and Kaňková, Kateřina},
article_location = {Berlin},
article_number = {1},
doi = {http://dx.doi.org/10.1515/cclm-2012-0833},
keywords = {advanced glycation end-products; diabetic nephropathy; fructosamine 3-kinase; glyoxalase; pentose phosphate pathway; transketolase},
language = {eng},
issn = {1434-6621},
journal = {Clinical Chemistry and Laboratory Medicine},
title = {Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality},
volume = {52},
year = {2014}
}
TY - JOUR
ID - 1092044
AU - Tanhäuserová, Veronika - Kuricová, Katarína - Pácal, Lukáš - Bartáková, Vendula - Řehořová, Jitka - Svojanovský, Jan - Olšovský, Jindřich - Bělobrádková, Jana - Kaňková, Kateřina
PY - 2014
TI - Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
JF - Clinical Chemistry and Laboratory Medicine
VL - 52
IS - 1
SP - 77-83
EP - 77-83
PB - Walter de Gruyter
SN - 14346621
KW - advanced glycation end-products
KW - diabetic nephropathy
KW - fructosamine 3-kinase
KW - glyoxalase
KW - pentose phosphate pathway
KW - transketolase
N2 - Background: We hypothesized that genetic variability in genes encoding enzymes metabolizing glycolytic intermediates produced in excess under hyperglycemic conditions [i.e., transketolase ( TKT ), transaldolase, TKT-like protein 1, fructosamine 3-kinase ( FN3K ), glyoxalase 1 and glucose-6-phosphate dehydrogenase] could influence progression of diabetic nephropathy (DN) and diabetesrelated morbidity and mortality. Methods: A total of 19 single nucleotide polymorphisms (SNPs) in six candidate genes were studied in 314 type 2 diabetic subjects with variable stage of kidney disease (normo- and microalbuminuria, proteinuria, end-stage renal disease). SNP selection criteria were based on known functional effect and gene coverage. SNPs were detected using polymerase chain reaction based methods. Subjects were followed up for median of 38 months. Time-to-event analysis considered three end-points: 1) DN progression by at least one stage; 2) major cardiovascular event; and 3) all-cause mortality. Results: We found combined effect of TKT SNP rs11130362 and FN3K SNP rs1056534 on DN progression (p < 0.01). Additionally, TKT rs3736156 alone and also in combination with the previous two SNPs exhibited significant effect on incidence of major cardiovascular events (p < 0.01 and p = 0.01, respectively). Conclusions: Genetic variability in rate-limiting enzymes of pathways proposed to confer hypothetical protection against hyperglycemia might act as an important determinant of hyperglycemia toxicity in long-standing diabetes.
ER -
TANHÄUSEROVÁ, Veronika, Katarína KURICOVÁ, Lukáš PÁCAL, Vendula BARTÁKOVÁ, Jitka ŘEHOŘOVÁ, Jan SVOJANOVSKÝ, Jindřich OLŠOVSKÝ, Jana BĚLOBRÁDKOVÁ a Kateřina KAŇKOVÁ. Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality. \textit{Clinical Chemistry and Laboratory Medicine}. Berlin: Walter de Gruyter, 2014, roč.~52, č.~1, s.~77-83. ISSN~1434-6621. Dostupné z: https://dx.doi.org/10.1515/cclm-2012-0833.
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