1022-7954/03/3906- $25.00 © 2003 MAIK “Nauka /Interperiodica” 0700 Russian Journal of Genetics, Vol. 39, No. 6, 2003, pp. 700–705. Translated from Genetika, Vol. 39, No. 6, 2003, pp. 840–846. Original Russian Text Copyright © 2003 by Marussin, Puzyrev, Salyukov, Bragina. INTRODUCTION Oxidative stress, i.e., an increase in formation of active oxygen forms and lipid peroxides (LPs), plays an important role in pathogenesis of a wide range of dis- eases [1–5]. The multicomponent, integrated and regu- lated antioxidant system (AOS) prevents uncontrolled free-radical oxidation (FRO) and maintains the optimal balance of redox reactions [6–11]. At present, the con- tribution of genetic factors into variation of the AOS parameters is studied. This may be related to the fact that the entire complex of interacting and interchange- able low- and high-molecular substances is difficult to analyze; moreover, the technical approaches used are often inadequate to assess the state of AOS. By using a single model system, it is impossible to assess unam- biguously and comprehensively all components of the antioxidant defense, such as scavenging free radicals, hydrogen and lipid peroxide degradation and restora- tion, binding metal ions that undergo valence changes and serve as potential catalytic agents for FRO, biomol- ecule repair after oxidative damage, and utilization of FRO products [12–14]. According to the literature data [15] and the results of our studies [16], about 50% of variation of the blood plasma antioxidant activity (AOA) is accounted for by additive effects of many genes. In view of that, the search for and specification of the AOS genetic determinants are of importance. We have studied the contribution of genetic varia- tion of transferrin (TF) and angiotensin-converting enzyme (ACE) to the population variation of the blood plasma AOA determined in the Fe 2+ –lecithin model system from the yield of the products interacting with thiobarbituric acid (TBA). The TF antioxidant effect results from binding iron ions. The AOA decreases with apoenzyme saturation with iron, though the complete saturation may lead, conversely, to generation of free radicals inducing the peroxide effect [6]. ACE does not belong to the antiox- idant enzymes. Nevertheless, its polymorphism may be associated with AOA variation, because of multiple physiological and biochemical ACE functions, the major of which is blood pressure regulation [17]. ACE regulates the content of angiotensin II, which increases the production of superoxide anions through NADP/NADPH-dependent oxidases [18, 19]. Of inter- est is the association between the insertion/deletion (I/D) polymorphism of the ACE gene (in the Alu repeat) and the content and activity of the enzyme in blood plasma [20, 21]. MATERIALS AND METHODS The blood plasma AOA was determined in the unre- lated subjects inhabiting the city of Seversk (75 males and 46 females) and Kargala village (38 males and 40 females) of the Tomsk oblast. The average age of the subjects examined was 52.88 ± 0.89 and 33.14 ± 1.29 years in the urban and rural populations, respec- tively. The samples of heparinized venous blood were taken during a period from October 1996 to June 1998. In the urban population, genotyping for the TF and ACE loci was conducted in 130 and 141 subjects, respectively, of which 102 and 111 subjects were exam- Correlation between Polymorphism of the Genes for Transferrin and Angiotensin-Converting Enzyme and Antioxidant Activity of Blood Plasma A. V. Marussin, V. P. Puzyrev, V. B. Salyukov, and E. Yu. Bragina Research Institute of Medical Genetics, Tomsk Research Center, Russian Academy of Medical Sciences, Tomsk, 634050 Russia; fax: (3822) 51-37-44; e-mail: marussin@img.tsu.ru Received March 13, 2002; in final form June 13, 2002 Abstract—In 75 male and 46 female subjects of an urban population (93% Russians) and in 38 males and 40 females of a rural population (87% Russians), the antioxidant activity (AOA) of blood plasma was deter- mined from the plasma ability to reduce the yield of products interacting with thiobarbituric acid in the model lecithin–Fe 2+ ion system. In the urban population, the loci TF (AvaI in exon5) and ACE (I/D polymorphism of the Alu repeat in intron16) were studied in 130 and 141 subjects, respectively. Of them, 102 and 111 subjects, respectively, were examined for AOA. In the rural population, the corresponding sample sizes were 75 and 76 (73 and 74 subjects were examined for AOA). The polymorphic loci of the urban and rural populations did not differ in the allele frequencies. In both populations Hardy–Weinberg and gametic equilibria were observed. The contributions of the TF and ACE genes to AOA variation in the combined sample from the urban and rural pop- ulations were 0.6 and 0.5%, respectively. HUMAN GENETICS