Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality

Veronika Tanhäuserová; Katarína Kuricová; Lukáš Pácal; Vendula Bartáková; Jitka Řehořová; Jan Svojanovský; Jindřich Olšovský; Jana Bělobrádková; Kateřina Kaňková

doi:10.1515/cclm-2012-0833

Article

Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality

Veronika Tanhäuserová , Katarína Kuricová , Lukáš Pácal , Vendula Bartáková , Jitka Řehořová , Jan Svojanovský , Jindřich Olšovský , Jana Bělobrádková and Kateřina Kaňková

Published/Copyright: March 13, 2013

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From the journal Clinical Chemistry and Laboratory Medicine Volume 52 Issue 1

Abstract

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 diabetes-related 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.

Keywords: advanced glycation end-products; diabetic nephropathy; fructosamine 3-kinase; glyoxalase; pentose phosphate pathway; transketolase

Corresponding author: Veronika Tanhäuserová, Faculty of Medicine, Department of Pathophysiology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic, Phone: +420 549 495443, Fax: +420 549 494340, E-mail: veronika.tan@mail.muni.cz

Study was supported by the grant NT13198 from the Ministry of Health of Czech Republic.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2012-11-30

Accepted: 2013-2-7

Published Online: 2013-03-13

Published in Print: 2014-01-01

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Articles in the same Issue

https://doi.org/10.1515/cclm-2012-0833

Keywords for this article

advanced glycation end-products; diabetic nephropathy; fructosamine 3-kinase; glyoxalase; pentose phosphate pathway; transketolase