DOI 10.1007/s10517-014-2717-4 Bulletin of Experimental Biology and Medicine, Vol. 158, No. 2, December, 2014

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GENERAL PATHOLOGY AND PATHOPHYSIOLOGY Lipid Peroxidation and Mitochondrial Superoxide Dismutase-2 Gene in Adolescents with Essential Hypertension T. A. Bairova, S. I. Kolesnikov, L. I. Kolesnikova, O. A. Pervushina, M. A. Darenskaya, and L. A. Grebenkina Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 158, No. 8, pp. 141-144, August, 2014 Original article submitted February 14, 2013 The study of LPO processes in adolescents of different races with essential hypertension revealed that Mongoloids exhibit oxidative stress by altering the level of the formation of diene conjugates, the primary LPO products. Caucasians increased the levels of both primary and end products of LPO, diene conjugates, and malondialdehyde. The revealed differences can be genetically determined because ethnic differences in the frequency of SOD2 gene Ala16Val polymorphism and its contribution to the biochemical phenotype were reported. The risk factors are Ala allele associated with increased MDA level for adolescent Caucasians and Val allele linked with decreased level of total antioxidant activity for adolescent Mongoloids. Key Words: essential arterial hypertension; superoxide dismutase; oxidative stress; gene; ethnos Essential hypertension (EH) is a multifactorial disease. Its onset and progression is determined by complex interactions of hemodynamic, neurohormonal, metabolic, and other systems [1]. In particular, dynamic balance in the LPO system and antioxidant system (AOS) underlies the function of systems regulating contraction of vascular smooth muscle cells and, therefore, systemic BP. The imbalance in the LPO–AOS system in adolescents with EH can lead to oxidative stress at the early stage of the pathological processes [5]. Furthermore, differences in LPO–AOS processes in EH are found in representatives of different ethnic groups, Buryats (Mongoloids) and Russians (Caucasians) [3]. Analysis of published reports showed that the imbalance in the LPO–AOS system can be genetically determined also by the fact that changes in activity Research Center of Family Health Problems and Human Reproduction, Siberian Division of Russian Academy of Medical Sciences, Irkutsk, Russia. Address for correspondence: [email protected]. T. A. Bairova

of antioxidant enzymes are based on genetic factors [4,7]. Superoxide dismutase 2 (SOD2) that catalyzes dismutation of superoxide anion to O2 and Н2O2, is one of the most important antioxidant enzymes. SOD2 is localized in the mitochondrial matrix. SOD2 gene encoding this enzyme is located in chromosome 6q25.3 and includes 5 exons (http://www.genecards.org). Ala16Val polymorphism is localized at the site responsible for binding to mitochondria to import the enzyme into the mitochondrial matrix. This site is cleaved in the mitochondrial matrix, and SOD is converted in an active form [8]. Activity of the Val-containing enzyme is 40% lower than that of the Ala-containing enzyme. In light of this, superoxide accumulates in the matrix carriers of the Val allele and Val /Val genotype, which leads to more severe oxidative damage to mitochondrial DNA [10]. This polymorphism was found to be a contributor to the development of cardiovascular disease [9,10]. Here we analyzed LPO–AOS processes in Caucasian and Mongoloid adolescents with EH and revealed

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Bulletin of Experimental Biology and Medicine, Vol. 158, No. 2, December, 2014 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY

relationships between LPO–AOS components with SOD2 gene, its Ala16Val polymorphism.

MATERIALS AND METHODS We surveyed 261 adolescents aged 14-17 years (mean age was 15.82±1.06 years). The main group comprised 142 adolescents, 102 Caucasians (Russians), and 40 Mongoloids (Buryats). The ethnicity data were collected by interviewing using a questionnaire including data on the nationality of their ancestors to the third generation. Persons related to each other were not included in the experimental group. Confirmed diagnosis of EH was the criterion for inclusion in the main group. Indicators of systolic and diastolic blood pressure 10-90 ‰ taking into account sex, age and body height were considered as normal. EH was diagnosed in adolescents with BP levels higher than 95 ‰ regarding sex, age, height and time index of systolic and/or diastolic BP higher than 25%. The control group included 119 adolescents (65 Caucasians and 54 Mongoloids) without family history of EH, with BP 10-90 ‰ regarding sex, age and height and without evidence of acute and/or exacerbation of chronic disease at the time of the survey. The work with adolescents has been conducted in full accordance with ethical principles of World Medical Association Declaration of Helsinki (2000). LPO intensity was assessed by the content of its products, diene conjugates (DC) and TBA-reactive products. Activity of AOS system was evaluated by total antioxidant activity [4] and SOD activity. The degree of imbalance between LPO and AOS systems was evaluated using the coefficient of oxidative stress calculated as the ratio of prooxidants and antioxidants at different LPO stages [6]. The coefficient of oxidative stress increases with enhancing LPO processes [2].

DNA was isolated from venous blood using DNAsorb-B kits (InterLabServis). PCR was carried out using Terzik automatic thermocycler. Reagent kits SNPEkspress Kardiogenetika (Litekh) were used for the amplification. The amplified products were detected in 3% agarose gel; the results of gel electrophoresis were visualized using a transilluminator and documented by photographing. The differences in the frequency of an allele or genotype of the polymorphism were compared using Pearson’s χ2 test with Yates correction. To compare LPO–AOS measures in adolescents-carriers of different genotypes, Kruskal–Wallis and Mann–Whitney tests were used. Differences were considered significant at p

Lipid peroxidation and mitochondrial superoxide dismutase-2 gene in adolescents with essential hypertension.

The study of LPO processes in adolescents of different races with essential hypertension revealed that Mongoloids exhibit oxidative stress by altering...
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