title: Chromosomal Aberrations and Exon 1 Mutation in the AKR1B1 Gene in Patients with Diabetic Neuropathy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biomolecules and Genetics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, India.
authors.forename: Radha
authors.initials: R
authors.lastname: Saraswathy
authors.affiliation: Biomolecules and Genetics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, India.
authors.forename: Sudhaa
authors.initials: S
authors.lastname: Anand
authors.affiliation: Consultant in Pain Medicine, Department of Anesthesiology, Epsom and St Helier University Hospitals NHS Trust, Carshalton, UK.
authors.forename: Sree Kumar
authors.initials: SK
authors.lastname: Kunnumpurath
authors.affiliation: Consultant Anaesthetist and Pain Medicine, Department of Anesthesiology, East Surrey Hospital, Red Hill, UK.
authors.forename: R Jones
authors.initials: RJ
authors.lastname: Kurian
authors.affiliation: Departments of Anesthesiology and Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA.
authors.forename: Alan David
authors.initials: AD
authors.lastname: Kaye
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT.
authors.forename: Nalini
authors.initials: N
authors.lastname: Vadivelu
keywords: Chromosome aberrations; diabetes mellitus; diabetic neuropathies–painful; exons; mutation