Publication details

Polymorphism in the pentose phosphate cycle enzymes as a modifier of hyperglycemia toxicity in diabetic nephropathy

Authors

PÁCAL Lukáš TANHÄUSEROVÁ Veronika KAŇKOVÁ Kateřina

Year of publication 2008
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description 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).
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info