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- Title
Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes.
- Authors
Ziegler, Dan; Schleicher, Erwin; Strom, Alexander; Knebel, Birgit; Fleming, Thomas; Nawroth, Peter; Häring, Hans‐Ulrich; Papanas, Nikolaos; Szendrödi, Julia; Müssig, Karsten; Al‐Hasani, Hadi; Roden, Michael; Häring, Hans-Ulrich; Szendrödi, Julia; Müssig, Karsten; Al-Hasani, Hadi; GDS Group
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
DIABETIC neuropathies; GENETIC polymorphisms; GENETIC techniques; TYPE 1 diabetes; NEURAL conduction; TYPE 2 diabetes; TRANSFERASES; CROSS-sectional method
- Publication
Diabetes/Metabolism Research & Reviews, 2017, Vol 33, Issue 4, pn/a
- ISSN
1520-7552
- Publication type
journal article
- DOI
10.1002/dmrr.2811