Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
-
Veronika Tanhäuserová
,
Katarína Kuricová
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.
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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Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Frontiers in research on the Maillard reaction in aging and chronic disease
- Reviews
- Role of the Maillard reaction in aging and age-related diseases. Studies at the cellular-molecular level
- Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review
- Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications
- Mini Reviews
- Post-translational modification derived products (PTMDPs): toxins in chronic diseases?
- Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes
- Augmentation of blood lipid glycation and lipid oxidation in diabetic patients
- Maillard reaction products: some considerations on their health effects
- The Maillard reaction and food allergies: is there a link?
- Perspectives
- Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma
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- Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
- General Clinical Chemistry and Laboratory Medicine
- Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen
- A new HPLC-based assay for the measurement of fructosamine-3-kinase (FN3K) and FN3K-related protein activity in human erythrocytes
- Increased circulating advanced glycation endproducts (AGEs) in acute trauma patients
- Circulating soluble RAGE increase after a cerebrovascular event
- Pentosidine determination in CSF: a potential biomarker of Alzheimer’s disease?
- Cardiovascular Diseases
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- Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure
- Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects
- Translational Research Papers
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- Formation of nitri- and nitrosylhemoglobin in systems modeling the Maillard reaction
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