Relationship between nerve conduction velocity with uncoupling protein 2 promoter polymorphism -866G/A and A allel frequency in type 2 diabetic patients with diabetic peripheral neuropathy

ABSTRACTRelationship between nerve conduction velocity with uncoupling protein 2promoter polymorphism -866G/A and A allel frequency in type 2 diabeticpatients with diabetic peripheral neuropathyDr. Z. Sebnem Aktaran, Residency thesis, Division of Endocrinology and MetabolismDisease, Coordinator: Prof. Dr. Ersin Akarsu, May 2007, 64 pagesProgression of the diabetic peripheral neuropathy (DPN) demonstrated differences inthe individual considered the contribution of genetic predisposition. We aim to studythe relationship between the -866G/A polymorphism in the promoter region of theuncoupling protein 2 (UCP2) which enhances transcriptional activity and A allelefrequency with nerve conduction velocities (NCV) and clinical factors. We compared370 type 2 diabetic patients with healthy control. Subjective neuropatic symptoms,neurologic examination and electrophysiologic measurements were evaluated.Diabetic patients were divided into two groups Group 1: (G/G) and Group 2:(G/A+A/A) according to genotype. Clinical features and NCV were compared andalso independent risk factors of the DPN were defined. The comparison of twoindependent group was performed with Mann Whitney U-test or Fisher?s Exact test.Relationship between NCV with UCP2 genotype and cinical factors assessed throughmultiple regression analysis (MRA) and ANOVA. Pearson correlation was performedfor correlation analysis. DPN was present in 46.2 % of the cases. DPN wassignificantly correlated with HbA1c, duration of DM, age at DM onset, retinopathy andnephropathy. The proportions of the individuals carrying genotype (-866G/A and A/A)and A allele frequency were significantly higher in the diabetic patients with DPN thanthat in the controls respectively (p<0.009, p<0.004). Group 2 had an early age at DMonset (p<0.0001) and high proportion of retinopathy (p=0.03). NCV was significantlylower in Group 2 than that in Group 1. MRA showed that UCP2 genotype and HbA1cwere related with the impairment of NCV independently of other clinical factors.HbA1C, and retinopathy. In conclusion, higher A allele frequency with DPN and earlyage at DM onset in the Turkish diabetic population might partly indicate the geneticpredisposition. Higher UCP2 activity related to A allel which was independent riskfactor in the impairment of NCV may contribute to reduce NCV via decreased ATPproduction in mitochondria. On the other hand, increased UCP2 in the DPN may be amarker of an inadequate antioxidant effect of the UCP2 in the chronic oxidativestress. Investigation of the genetic tendency for DPN may guide to define the riskfactors and also in the new insights for the treatment.Key words: UCPs, Diabetic peripheral neuropathy, Oxidative stress, Genepolymorphism