615 0007-4888/16/1625-0615 © 2017 Springer Science+Business Media New York Association of Glu298Asp Polymorphism of Endothelial NO Synthase Gene with Metabolic Syndrome Development: a Pilot Study N. S. Fattakhov 1,3 , D. A. Skuratovskaya 1 , M. A. Vasilenko 1 , E. V. Kirienkova 1 , P. A. Zatolokin 2 , N. I. Mironyuk 2 , and L. S. Litvinova 1 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 162, No. 11, pp. 563-566, November, 2016 Original article submitted February 18, 2016 We studied association of single nucleotide polymorphism Glu298Asp (rs1799983) of the NOS3 gene with the risk of metabolic syndrome in the Slavic population. Blood samples were obtained from 128 patients with metabolic syndrome and 100 healthy individuals. Poly- morphism Glu298Asp of the NOS3 gene was genotyped by allele-specific PCR. Allele Asp (OR=1.95, 95%CI 1.29-2.95, p=0.007) and genotype Asp/Asp (OR=2.56, 95%CI 0.98-6.72, p=0.04) were associated with the risk of metabolic syndrome in Slavic population. Patients with metabolic syndrome carrying genotype Asp/Asp had higher serum endothelin-1 level in comparison with Glu/Asp and Glu/Glu carriers. Key Words: metabolic syndrome; single nucleotide polymorphism; nitric oxide; endothelial NO synthase; endothelial dysfunction 1 Immanuel Kant Baltic Federal University; 2 Regional Hospital of the Kaliningrad Region, Kaliningrad; 3 Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia. Address for correspondence: nikola. fattahov@mail.ru. N. S. Fattakhov Metabolic syndrome (MetS) is a cluster of factors of increased risk of cardiovascular diseases and type 2 diabetes. According to definition proposed by the In- ternational Diabetes Federation (2005), MetS is char- acterized by abdominal obesity combined with at least two of the following disorders: elevated triglyceride content, reduced HDL level, fasting hyperglycemia, and high BP. All MetS components have adverse ef- fects on the endothelium and promote endothelial dys- function (ED), which plays a key role in atheroscle- rosis pathogenesis and can increase the risk of type 2 diabetes [15]. Endothelial NO synthase (eNOS) is involved in production of NO, a potent vasodilator responsible for normal endothelial function mainte- nance [1]. Studies on animal models have shown that the absence of eNOS results in development of insulin resistance, hypertriglyceridaemia, and hypertension, i.e. MetS phenotypes [4]. In the human body, eNOS is encoded by the NOS3 gene located in chromosome 7q35-36. In the NOS3 gene, several polymorphisms have been identi- fied. Polymorphism Glu298Asp (G894T, rs1799983) in the coding region of the gene is of particular in- terest: it leads to guanine substitution for thymine in exon 7 and corresponding glutamine amino acid substitution for aspartic acid at position 298, and thereby it affects functioning of the enzyme. Associa- tion of Glu298Asp with increased risk of cardiovas- cular disease, NO synthesis, and ED was described in different populations [13]. The aim of this study was to investigate asso- ciation of functional polymorphism Glu298Asp of the NOS3 gene with MetS risk in the Slavic population. MATERIALS AND METHODS The study involved 128 patients with MetS (48 men and 80 women, mean age 44.2±8.5 years), treated in the Regional Hospital of Kaliningrad Region. All pa- tients signed free and informed consent. The control group included 100 apparently healthy people (48 Bulletin of Experimental Biology and Medicine, Vol. 162, No. 11, March, 2017 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY DOI 10.1007/s10517-017-3670-9