Detailed Information on Publication Record
2007
Transketolase (TKT) gene variability as a potencial susceptibility factor for diabetic nephropathy
PÁCAL, Lukáš, Andrea STEJSKALOVÁ, Veronika TANHÄUSEROVÁ and Kateřina KAŇKOVÁBasic information
Original name
Transketolase (TKT) gene variability as a potencial susceptibility factor for diabetic nephropathy
Name in Czech
Transketolase (TKT) gene variability as a potencial susceptibility factor for diabetic nephropathy
Authors
PÁCAL, Lukáš (203 Czech Republic, guarantor), Andrea STEJSKALOVÁ (203 Czech Republic), Veronika TANHÄUSEROVÁ (203 Czech Republic) and Kateřina KAŇKOVÁ (203 Czech Republic)
Edition
20th Annual Meeting Edinburgh, Scotland, May 11 - 12, 2007, 2007
Other information
Language
English
Type of outcome
Konferenční abstrakt
Field of Study
30202 Endocrinology and metabolism
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
není předmětem státního či obchodního tajemství
RIV identification code
RIV/00216224:14110/07:00019057
Organization unit
Faculty of Medicine
Keywords in English
transketolase; polymorphism; diabetic nephropathy
Tags
International impact, Reviewed
Změněno: 2/4/2010 15:08, prof. MUDr. Kateřina Kaňková, Ph.D.
V originále
Objective: Accumulation of proximal glycolytic intermediates - due to the allosteric inhibition of enzymes, changed NADH/NAD+ ratio and modification of the glycolytic enzyme glyceraldehyd-3-phosphate dehydrogenase provides substrates for the metabolic pathways plays contributing to the pathogenesis of diabetic complications (such as formation of Advanced Glycation End-products (AGEs), polyols, hexosamines etc.). Pentose phosphate pathway (PPP) represents potentially "protective" mechanism in hyperglycemia since shunting of cumulated glycolytic intermediates (esp. triosephosphates) into the PPP reactions supposedly "disburdens" glycolysis and quantitatively limits processing of glycolytic intermediates in the alternative metabolic pathways. We hypothesized that genetic variability in the rate-limiting enzyme of the PPP non-oxidative branch - transketolase - contributes to an interindividual variability in the onset and progression of diabetic nephropathy (DN). Subjects and Methods: Study comprised 421 subjects (204 DM non-DN and 217 DM+DN subjects) In the first phase, SNPs with MAF >10% in the Caucasian population were selected with the density 1 per haplotype block (htSNPs) in the TKT gene (MIM no. 606781, chrom. 3p14.3). In pilot experiments those with high pair-wise LD were excluded, remaining 6 SNPs (rs2279323, rs3736156, rs1051483, rs12487632, rs968702 and rs13101181) to be genotyped in the whole study sample. SNPs were detected by means of polymerase chain reaction (PCR) using fluorescent-labelled probes (TaqMan, Applied Biosystems). Haplotypes were constructed based on genotype data using Bayesian algorithm (PHASE). Differences in haplotype frequencies between the groups will be tested by permutation testing. Logistic regression (incl. input variables such as age and gender, DM duration, fasting glycemia, HbA1c, microalbuminuria, proteinuria and GFR), survival analysis (Kaplan-Meier) and Cox proportional hazard regression were used to assess the risk of disease-associated haplotypes. Conclusions: Results suggest that TKT variability might play a role in the individual susceptibility to the development of DN.
In Czech
Objective: Accumulation of proximal glycolytic intermediates - due to the allosteric inhibition of enzymes, changed NADH/NAD+ ratio and modification of the glycolytic enzyme glyceraldehyd-3-phosphate dehydrogenase provides substrates for the metabolic pathways plays contributing to the pathogenesis of diabetic complications (such as formation of Advanced Glycation End-products (AGEs), polyols, hexosamines etc.). Pentose phosphate pathway (PPP) represents potentially "protective" mechanism in hyperglycemia since shunting of cumulated glycolytic intermediates (esp. triosephosphates) into the PPP reactions supposedly "disburdens" glycolysis and quantitatively limits processing of glycolytic intermediates in the alternative metabolic pathways. We hypothesized that genetic variability in the rate-limiting enzyme of the PPP non-oxidative branch - transketolase - contributes to an interindividual variability in the onset and progression of diabetic nephropathy (DN). Subjects and Methods: Study comprised 421 subjects (204 DM non-DN and 217 DM+DN subjects) In the first phase, SNPs with MAF >10% in the Caucasian population were selected with the density 1 per haplotype block (htSNPs) in the TKT gene (MIM no. 606781, chrom. 3p14.3). In pilot experiments those with high pair-wise LD were excluded, remaining 6 SNPs (rs2279323, rs3736156, rs1051483, rs12487632, rs968702 and rs13101181) to be genotyped in the whole study sample. SNPs were detected by means of polymerase chain reaction (PCR) using fluorescent-labelled probes (TaqMan, Applied Biosystems). Haplotypes were constructed based on genotype data using Bayesian algorithm (PHASE). Differences in haplotype frequencies between the groups will be tested by permutation testing. Logistic regression (incl. input variables such as age and gender, DM duration, fasting glycemia, HbA1c, microalbuminuria, proteinuria and GFR), survival analysis (Kaplan-Meier) and Cox proportional hazard regression were used to assess the risk of disease-associated haplotypes. Conclusions: Results suggest that TKT variability might play a role in the individual susceptibility to the development of DN.
Links
| NR9443, research and development project |
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