Polymorphism in the pentose phosphate cycle enzymes as a modifier of hyperglycemia toxicity in diabetic nephropathy
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| Year of publication | 2008 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| 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). |
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