Chromosomal Aberrations and Exon 1 Mutation in the AKR1B1 Gene in Patients with Diabetic Neuropathy

Recent decades have seen an increase in our understanding of a number of pathophysiological processes associated with type 2 diabetes mellitus (DM). Despite increases in understanding and treatment options, diabetic neuropathy remains a significant problem and is associated with tremendous morbidity and mortality. In this regard, oxidative DNA damage is postulated to play a role in diabetes-mediated neuropathic pathogenesis.

In this pilot investigation, we studied the extent of chromosomal damage utilizing chromosomal aberration (CA) assay in cultured lymphocytes of patients in 3 subgroups: patients with diabetic neuropathy, patients with type 2 DM and no neuropathy, and a control group.

The patients with diabetic neuropathy showed a statistically significantly higher rate of CA (P<0.001, 0.086 ± 0.04) compared to the DM patients without neuropathy (0.03 ± 0.02). Samples from subjects with diabetic neuropathy were evaluated to check for mutations in the AKR1B1 gene (exon 1). A significant number of mutations appeared after DNA sequencing within the AKR1B1 gene. Of 50 diabetic neuropathy patient samples analyzed, 10 revealed mutations.

Our results suggest that painful diabetic neuropathy is a condition with enhanced genomic instability characterized by increased CA and possible mutations. Exon 1 of the gene AKR1B1 showed significant mutations in patients with painful diabetic neuropathy.