0026-8933/04/3802- © 2004 MAIK “Nauka / Interperiodica” 0200 Molecular Biology, Vol. 38, No. 2, 2004, pp. 200–204. Translated from Molekulyarnaya Biologiya, Vol. 38, No. 2, 2004, pp. 244–249. Original Russian Text Copyright © 2004 by Zotova, Savost’yanov, Chistyakov, Bursa, Galeev, Strokov, Nosikov. INTRODUCTION Diabetic polyneuropathy (DPN) is a late vascular complication of diabetes mellitus (DM), and results from damage to the nervous tissue. Peripheral nerve sensitivity, conduction of the nervous impulse, and blood supply to the brain and nerves are impaired because of a decrease in circulation rate and dysfunc- tion of the vascular endothelium. Oxidative stress, which is a consequence of long-term hyperglycemia, is considered a major cause of these alterations. In DM, elevated serum glucose increases the con- centration of glucose in various cells and tissues, including endothelium and neurons. In turn, elevated cell glucose activates glycolysis and the tricarboxylic acid cycle and, consequently, increases the concentra- tion gradient of protons across the inner mitochondrial membrane [1, 2]. When the membrane potential exceeds a certain threshold, superoxide radicals, which are by-products of oxidative phosphorylation, are generated at a far greater rate. In hyperglycemia, their contents in mitochondria and cytoplasm substan- tially increase, which expedites generation of other free radicals and peroxidation products [1, 2]. This is the major cause of irreversible changes that take place in mitochondria of neurons and endothelial cells and include mitochondrial DNA damage, dysfunction of enzymatic complexes involved in ATP synthesis, and, eventually, a substantial drop in production of energy necessary for efficient cell functioning. In addition, oxidative stress is the major cause of rapid oxidation of membrane lipids; this disrupts the structure of the myelinic envelope of nerves, impairs their integrity, and leads to myelinopathy [3]. In the course of evolution, eukaryotes have acquired several types of enzymes to neutralize free radicals and peroxides. The major antioxidant enzymes are superoxide dismutases [EC 1.15.1.1], catalase [EC 1.11.1.6], glutathione reductase [EC 1.6.4.2], glutatione peroxidase [EC 1.11.1.9], and glu- tathione S-transferases [EC 2.5.1.18]. Catalase is one of the key antioxidant enzymes. In peroxisomes of hepatocytes, renal cells, and erythro- cytes, the enzyme decomposes hydrogen peroxide into water and free oxygen. In the cell cytoplasm, a similar reaction is carried out by glutathione peroxi- dase [4]: 2ç 2 é 2 2ç 2 é + é 2 ç 2 é 2 + 2G–SH 2ç 2 é + G–S–S–G. Glutathione S-transferases are related enzymes involved in metabolizing a broad variety of xenobiot- GENOMICS. TRANSCRIPTOMICS. PROTEOMICS Association of Polymorphic Markers of the Antioxidant Enzyme Genes with Diabetic Polyneuropathy in Type 1 Diabetes Mellitus E. V. Zotova 1 , K. V. Savost’yanov 1 , D. A. Chistyakov 1 , T. R. Bursa 2 , I. V. Galeev 2 , I. A. Strokov 2 , and V. V. Nosikov 1 1 State Research Center GosNIIGenetika, Moscow, 117545 Russia E-mail: lena-zotova@mail.ru; nosikov@genetika.ru 2 Department of Endocrinology and Diabetology, Russian Medical Academy of Postgraduate Education, WHO Center of Informatics in Diabetes, Moscow, 125315 Russia Received June 20, 2003 Abstract—The allele and genotype frequency distributions of polymorphic markers of genes coding for anti- oxidant enzymes were compared for type 1 diabetes mellitus patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients) had nonoverlapping (polar) phenotypes. Group DPN+ included 86 patients with DPN and diabetic record no more than 5 years. Control group DPN– included patients without DPN and diabetic record of at least 10 years. Comparative analysis with Fisher’s exact test revealed a significant difference in allele and genotype frequency distributions of the í(–262)ë polymorphic marker of the CAT gene. Polymorphic markers C1167T of the CAT gene, Pro/Leu of the GPX1 gene, 0/+ of the GSTT1 gene, and 0/+ of the GSTM1 gene showed no significant difference in allele or genotype frequency distribution. On this evi- dence, these markers were not associated with DPN in the sample examined. Key words: type 1 diabetes mellitus, diabetic polyneuropathy, oxidative stress, catalase, glutathione peroxidase, glutathione S-transferase, polymerase chain reaction, human UDC 575.113.2