Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes - PubMed (original) (raw)

doi: 10.1002/dmrr.2811. Epub 2016 May 15.

Dan Ziegler 1 2 3, Erwin Schleicher 3 4 5, Birgit Knebel 3 6, Thomas Fleming 3 7, Peter Nawroth 3 7, Hans-Ulrich Häring 3 4 5, Nikolaos Papanas 8, Julia Szendrödi 1 2 3, Karsten Müssig 1 2 3, Hadi Al-Hasani 3 6, Michael Roden 1 2 3; GDS Group 9

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Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes

Dan Ziegler et al. Diabetes Metab Res Rev. 2017 May.

Abstract

Background: Shunting of glycolytic intermediates into the pentose phosphate pathway has been suggested to protect from hyperglycaemia-induced microvascular damage. We hypothesized that genetic variability in the gene encoding transketolase, a key pentose phosphate pathway enzyme, contributes to early nerve dysfunction in recent-onset diabetes.

Methods: In this cross-sectional study, we assessed nine single nucleotide polymorphisms (SNPs) in the transketolase gene, plasma methylglyoxal concentrations, and clinical and quantitative measures of peripheral nerve function in 165 type 1 and 373 type 2 diabetic patients with a diabetes duration up to 1 year.

Results: The Total Symptom Score was associated with transketolase SNPs rs7648309, rs62255988, and rs7633966, while peroneal motor nerve conduction velocity (MNCV) correlated only with rs7648309 (P < 0.01). Cold thermal detection threshold (TDT) (foot) was associated with transketolase SNPs rs11130362 and rs7648309, while warm TDT (hand) correlated with rs62255988 and rs7648309 (P < 0.01). After Bonferroni correction, the correlations of transketolase SNP rs7648309 with Total Symptom Score and rs62255988 with warm TDT (hand) remained statistically significant. Among subgroups, men with type 2 diabetes showed the strongest associations. No associations were observed between each of the nine tagged transketolase SNPs and plasma methylglyoxal concentrations.

Conclusions: The observed associations of genetic variation in transketolase enzyme with neuropathic symptoms and reduced thermal sensation in recent-onset diabetes suggest a role of pathways metabolizing glycolytic intermediates in early diabetic neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: diabetic polyneuropathy; nerve conduction velocity; neuropathic symptoms; single nucleotide polymorphisms; thermal detection thresholds; transketolase.

Copyright © 2016 John Wiley & Sons, Ltd.

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