767 0007-4888/19/16760767--©-2019--Springer-Science+Business-Media,-LLC Bulletin  of  Experimental  Biology  and  Medicine,  Vol.  167,  No.  6,  October, 2019 GENETICS Gene Polymorphism of Xenobiotic Biotransformation Enzymes in Patients with Classical Ph-Negative Myeloproliferative Neoplasms V. A. Ovsepyan, E. V. Tregubova, A. S. Luchinin, and N. V. Minaeva Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 6, pp. 726-730, June, 2019 Original article submitted November 14, 2018 The correlation of gene polymorphisms rs4025935 (large deletion), rs1695 (313A>G), rs71748309 (large deletion), and rs1800566 (609C>T) of GSTM1, GSTT1, and NQO1 genes encoding glutathione-S-transferases (GST) M1, P1, and T1 and NADPH-quinone oxidore- ductase with the risk of development of classical Ph-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofbrosis) was studied in the Caucasian ethnicity population of Vyatka region of the Russian Federation. It was found that NQO1*609T allele, NQO1*609T genotypes, and homozygous carriage of a deletion (null) allele of GSTT1 gene are associated with the risk of development of myeloproliferative neoplasms (OR=1.29, 95%CI=1.02-1.64, p=0.04; OR=1.39, 95%CI=1.04-1.85, p=0.03; and OR=1.48, 95%CI=1.03-2.12, p=0.03, respectively). However, no infuence of GSTM1 and GSTP1 gene polymorphisms on the risk of development of myeloproliferative disorders was registered. Key Words: Ph-negative myeloproliferative neoplasms; GSTM1, GSTP1, GSTT1, and NQO1 genes; polymorphisms Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency of the Russian Federation, Kirov, Russia. Address for correspondence: vovsepyan@mail.ru. V. A. Ovsepyan Classical Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera, essential throm- bocythemia, and primary myelofbrosis are clonal dis- orders characterized by proliferation of one or several cell lines of myelopoiesis in the bone marrow with the signs of preserved terminal differentiation and as- sociated with changes in blood parameters. Despite recent advances in deciphering molecular and genetic mechanisms of these disorders, the initial mutation inducing malignization of hemopoietic cells is not identifed. Little is known about the etiology of the disease. The main hypothesis considers the polyetio- logical pattern of the disorders suggesting that suscep- tibility to MPN is realized under the effect of external factors damaging the cell genome and inducing ma- lignant transformation [4,7,13]. Driver mutations of JAK2 (V617F and exon 12), MPL, and CARL genes observed in the majority of patients play an important role in the pathogenesis of these Ph-negative MPN [13]. However, there is growing evidence that consti- tutive parameters of the genome, in particular poly- morphisms of the key enzymes of phase II biotrans- formation of xenobiotics (GSTM1, GSTP1, GSTT1, and NQO1) involved in detoxifcation of a variety of exogenous and endogenous genotoxicants that can damage cell genome, play a role in the pathogenesis of malignant neoplasms [2,3,5,6,8-10,12,14,15]. Pub- lished data suggest that functionally relevant single- nucleotide polymorphisms 313A>G and 609C>T of DOI 10.1007/s10517-019-04619-5