THE RELATIONSHIP BETWEEN THE FREQUENCY OF CONGENITAL MALFORMATIONS IN NEWBORNS OF WOMEN RESIDING IN AN INDUSTRIAL REGION WITH THE POLYMORPHISM OF THE GENES OF THE BIOTRANSFORMATION SYSTEM
Introduction. There is a number of polymorphic genes, the products of which take part in the biotransformation process and possess of the different activity. As a result of an imbalance in the processes of xenobiotic biotransformation, there is occurred an accumulation of toxic electrophilic compounds, the rise in a mutagenic activity, that can be very important in the formation of congenital malformations. Therefore, the study of the association of gene polymorphisms of the first and second phases of biotransformation with various congenital malformations is topical. The aim of the study. To investigate the role of the polymorphism of genes of the xenobiotic biotransformation system (CYP1A2*1F, GSTT1, GSTM1) encoding the enzymes I and II detoxification phases in women with the complicated obstetric history, residing in an industrial region. Material and methods. A survey of 53 women of reproductive age living in the territory of Novokuznetsk was carried out. The comparison group (the control) consisted of 27 women. These women did not have spontaneous miscarriages, and they carried the fetus to term without congenital malformations. The study group included 26 women who gave birth to babies with congenital malformations. Genomic DNA was isolated by the phenol-chloroform extraction method followed by the ethanol precipitation. The molecular and genetic analysis of the gene polymorphism of cytochrome 1A2 (CYP1A2), glutathione S-transferase τ-1 (GSTT1) and glutathione S-transferase μ-1 (GSTM1) was carried out using Real-Time mode. Results. A high risk of congenital fetal malformations in women with the A/A CYP1A2*1F genotype and resistance to these pathologies in the presence of a heterozygous form of the gene C/A CYP1A2*1F was revealed. The relationship between the high risk of stillbirth due to the placental insufficiency in women with deletion polymorphism of the gene GSTM1 “-”, while the normal functioning gene GSTM1 “+” was associated with the resistance to antenatal fetal death.
About the authorsGulyaeva Olga N.
Gudinova Zh.V. The problem of identifying the causes for the formation of children’s disability in the regions of the Russian Federation. Zdorov’ye naseleniya i sreda obitaniya. 2004; (9): 29-34. (in Russian)
Demikova N.S., Lapina A.S. Congenital malformations in the regions of the Russian Federation: Result of monitoring in 2000-2010. Rossiyskiy vestnik perinatologii i pediatrii. 2012; 57(2): 91-8. (in Russian)
Antonov O.V. Problems and prospects of monitoring congenital malformations in children. Problemy sotsial’noy gigiyeny, zdravookhraneniya i istorii meditsiny. 2007; (1): 6-8. (in Russian)
Towbin J.A., Casey B., Belmont J. The molecular basis of vascular disorders. Am. J. Hum. Genet. 1999; 64 (3): 678-84.
Woolf A.S., Winyard P.J.D. Molecular mechanisms of human embryogenesis: developmental pathogenesis of renal tract malformations. Pediatric and Developmental Pathology. 2002; 5 (2): 108-29.
Durnev A.D. Prevention of induced mutagenesis. Meditsinskaya genetika. 2005; 4 (4): 123. (in Russian)
Mogilenkova L.A., Rembovskiy V.R. Role of genetic polymorphism and differences in the detoxification of chemical substances in the human body. Gigiena i sanitariya. 2016; 95 (3): 255-62. DOI: 10.18821/0016-9900-2016-95-3-255-262. (in Russian)
Antonova I.V., Bogacheva E.V., Kitaeva Yu.Yu. Role of exogenous factors in malformation forming (review). Ekologiya cheloveka. 2010; (6): 30-5. (in Russian)
Gulyaeva L.F., Vavilin V.А., Lyakhovich V.V. Xenobiotic biotransformation enzymes in chemical cancerogenesis [Fermenty biotransformatsii ksenobiotikov v khimicheskom kantserogeneze]. Novosibirsk; 2000. (in Russian)
Schmidt R.J., Romitti P.A., Burns T.L., Murray J.C., Browne M.L., Druschel C.M., Olney R.S. Caffeine, Selected Metabolic Gene Variants, and Risk for Neural Tube Defects. Birth Defects Res. A Clin. Mol. Teratol. 2010; 88 (7): 560-9. Doi: 10.1002/bdra.20681.
Sata F., Yamada H., Suzuki K., Saijo Y., Kato E.H., Morikawa M. et al. Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss. Mol. Hum. Reprod. 2005; 11 (5): 357-60.
Grosso L.M., Triche E.W., Belanger K., Benowitz N.L., Holford T.R., Bracken M. B. Caffeine metabolites in umbilical cord blood, cytochrome P-450 1A2 activity, and intrauterine growth restriction. Am. J. Epidemiol. 2006; 163 (11): 1035-41.
Hallström H., Melhus H., Glynn A., Lind L., Syvänen A.C., Michaëlsson K. Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study. Nutr. Metab. (London ). 2010; 7: 12. Cited 07.09.2015. DOI: 10.1186/1743-7075-7-12.
Gorgeeva L.A., Glushkova O.A., Ermolenko N.A., Popova O.S., Gareeva Ju.V., Shatalina I.V. et al. Combinations of maternal polymorphismis of CYP1A2*1F and GST in congential malformations in the fetus and newborn. Meditsinskaya genetika. 2011; 10 (11): 9-15. (in Russian)
Glushkova O.A., Gordeeva L.A., Shatalina I.V., Ermolenko N.A., Popova O.S., Gareeva Yu.V. et al. Association of maternal polymorphisms of genes CYPIA2*1F and GST and their combination of congenital malformations in fetus and newborn. Molekulyarnaya meditsina. 2012; (2): 39-46. (in Russian)
Shatalina I.V., Gordeeva L.A., Voronina E.N., Popova O.S., Sokolova E.A., Ermolenko N.A. et al. Association of smoking, maternal polymorphic variants of genes GST loci M1 and T1 with a predisposition to congenital malformations in the child. Meditsina v Kuzbasse. 2014; 13 (3): 56-60. (in Russian)
Mikhaylin E.S., Ivashchenko T.E., Baranov V.S., Aylamazyan E.K. The estimation of the frequencies of GSTT1 and GSTM1 0/0 genotype in case of gestosis. Zhurnal akusherstva i zhenskikh bolezney. 2010; LIX (6): 79-85. (in Russian)
Sidorova I.S., Unanian A.L. Miscarriage: impaired antioxidant protection and its correction. Rossiyskiy vestnik akushera-ginekologa. 2009; 9 (1): 14-6. (in Russian)
Grigoryev Yu.A., Soboleva S.V. Reproductive health as a factor of the reduced birth rates in Siberia. Region: Ekonomika i Sotsiologiya. 2013; (2): 215-36. (in Russian)
Sidelnikova V.M. Recurrent pregnancy loss - a modern view of the problem. Akusherstvo i ginekologiya. 2007; (5): 24-7. (in Russian)
Bespalova O.N., Ivaschenko T.E., Tarasenko O.A., Malisheva O.V., Baranov V.S., Aylamazyan E.K. Association of glutathione-S-transferase genes М1, Т1, Р1 polymorphism with placental insufficiency. Zhurnal akusherstva i zhenskikh bolezney. 2006; LV (2): 25-31. (in Russian)
Morales E., Sunyer J., Castro-Giner F., Estivill X., Julvez J., Ribas-Fitó N. et al. Influence of glutathione S-transferase polymorphisms on cognitive functioning effects induced by p,p’-DDT among preschoolers. Environ Health Perspect. 2008; 116 (11): 1581-85. Doi: 10.1289/ehp.11303.
Gulyayeva O.N., Kazitskaya A.S., Renge L.V., Alekseyeva M.V., Yadykina T.K., Zhukova A.G. Influence of polymorphisms of the genes of the xenobiotic biotransformation system on the formation of congenital malformations of the fetus in the women living in the environmentally unfavourable region. In: Ecological and socio-hygienic aspects of the health of the population of Siberia: Materials of the conference and seminar [Ekologicheskiye i sotsial’no-gigiyenicheskiye aspekty zdorov’ya naseleniya Sibiri: Materialy konferentsii i seminara]. Novokuznetsk; 2017: 85-8. (in Russian)
Morales E., Sunyer J., Julvez J., Castro-Giner F., Estivill X., Torrent M., De Cid R. GSTM1 polymorphisms modify the effect of maternal smoking during pregnancy on cognitive functioning in preschoolers. J. Epidemiol. 2009; 38 (3): 690-7. DOI.org/10.1093/ije/dyp141.
Ferreira de Almeida T., Bertola D.R. Microdeletion 11q13.1.q13.2 in a patient presenting with developmental delay, facial dysmorphism, and esophageal atresia: Possible role of the GSTP1 gene in esophagus malformation. Birth Defects Research. Part A: Clinical and Molecular Teratology. 2013; 97: 463-66. DOI:10.1002/bdra.23115
Sambrook J., Fritsch E.F., Maniatis T. Molecular cloning: a laboratory manual. In 3 volumes. 2nd Ed. NY.: Cold Spring Harbor Laboratory Press; 1989.
Spitsyn V.A. Biochemical human polymorphism (anthropological aspects). [Biokhimicheskiy polimorfizm cheloveka (antropologicheskie aspekty)]. Moscow: Moscow State University; 1985. (in Russian)
Artamonova V.G. Actual problems of industrial ecology and prevention of occupational diseases. Vestnik RAMN. 1998; (1): 38-42. (in Russian)
Tracy T.S., Venkataramanan R., Glover D.D., Caritis S.N. Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy. Am. J. Obstet. Gynecol. 2005; 192 (2): 633-39. DOI: https://doi.org/10.1016/j.ajog.2004.08.030
Schmidt R.J., Romitti P.A., Burns T.L., Murray J.C., Browne M.L., Druschel C.M., Olney R.S. Caffeine, selected metabolic gene variants, and risk for neural tube defects. Birth Defects Research. Part A: Clinical and Molecular Teratology. 2010; 88: 560-69. DOI:10.1002/bdra.20681
Hong Y.C., Lee K.H., Yi C.H., Ha E.H., Christiani D.C. Genetic susceptibility of term pregnant women to oxidative damage. Toxicol. Lett. 2002; 129 (3): 255-262. DOI.org/10.1016/S0378-4274(02)00014-0
- Refbacks are not listed
Контент доступен под лицензией Creative Commons Attribution 3.0 License.