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

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.