2008
Polymorphism in the pentose phosphate cycle enzymes as a modifier of hyperglycemia toxicity in diabetic nephropathy
PÁCAL, Lukáš, Veronika TANHÄUSEROVÁ a Kateřina KAŇKOVÁZákladní údaje
Originální název
Polymorphism in the pentose phosphate cycle enzymes as a modifier of hyperglycemia toxicity in diabetic nephropathy
Název česky
Polymorphism in the pentose phosphate cycle enzymes as a modifier of hyperglycemia toxicity in diabetic nephropathy
Autoři
PÁCAL, Lukáš, Veronika TANHÄUSEROVÁ a Kateřina KAŇKOVÁ
Vydání
Molecular mechanisms of glucolipotoxicity in diabetes, 2008
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Obor
30202 Endocrinology and metabolism
Stát vydavatele
Irsko
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Lékařská fakulta
Klíčová slova anglicky
pentose phosphate pathway; transketolase; nephropathy; hypeglycemia
Příznaky
Mezinárodní význam
Změněno: 2. 2. 2009 12:34, prof. MUDr. Kateřina Kaňková, Ph.D.
V originále
Introduction: We hypothesized that genetic variability in the key enzymes of non-oxidative and oxidative branches of pentose phosphate pathway (transketolase, transaldolase, TKT-like and glucose-6-phosphatedehydrogenase) - a potentially "protective" mechanism in hyperglycemia - can contribute to an interindividual variability in the onset and progression of diabetic nephropathy (DN). Methods: A total of 12 SNPs with MAF higher than 10% located in different haplotype blocks were genotyped by means of PCR. Haplotypes were inferred using Bayesian-based algorithm. A total of 434 T2DM subjects were included in the association study (cases were subjects with DN; controls were gender- and age-matched diabetics without DN, ~1:1). Results: Haplotype distribution of TKT differed significantly between DN vs. non-DN groups (P=0.046, 10 000 permutations). Common haplotype with frequency 0.22 in the whole study population was identified as a risk-haplotype (OR=2.1). Carrier state of the risk-haplotype was associated with significantly accelerated onset of DN (P=0.05, Kaplan-Meier). Conclusions: Results suggest that TKT variability might play a role in the individual susceptibility to DN. This finding might be an important determinator of the benefit from the treatment with lipid-soluble TKT activator (benfothiamin).
Česky
Introduction: We hypothesized that genetic variability in the key enzymes of non-oxidative and oxidative branches of pentose phosphate pathway (transketolase, transaldolase, TKT-like and glucose-6-phosphatedehydrogenase) - a potentially "protective" mechanism in hyperglycemia - can contribute to an interindividual variability in the onset and progression of diabetic nephropathy (DN). Methods: A total of 12 SNPs with MAF higher than 10% located in different haplotype blocks were genotyped by means of PCR. Haplotypes were inferred using Bayesian-based algorithm. A total of 434 T2DM subjects were included in the association study (cases were subjects with DN; controls were gender- and age-matched diabetics without DN, ~1:1). Results: Haplotype distribution of TKT differed significantly between DN vs. non-DN groups (P=0.046, 10 000 permutations). Common haplotype with frequency 0.22 in the whole study population was identified as a risk-haplotype (OR=2.1). Carrier state of the risk-haplotype was associated with significantly accelerated onset of DN (P=0.05, Kaplan-Meier). Conclusions: Results suggest that TKT variability might play a role in the individual susceptibility to DN. This finding might be an important determinator of the benefit from the treatment with lipid-soluble TKT activator (benfothiamin).
Návaznosti
| NR9443, projekt VaV |
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