ASSOCIATIONS OF CANDIDATE GENES IN THE FORMATION OF UTERINE FIBROIDS

DOI: https://doi.org/None

O.B. Altukhova (1), I.V. Ponomarenko (1), N.A. Demakova (1), K.I. Prashchayev (2,3), M.I. Churnosov (1), G.G. Shaginyan (2) 1 -Belgorod National Research University, Pobedy str., 85, Belgorod, 308015, Russian Federation; 2 -Research medical center «Gerontology», Aeroportovskaya str., bld. 4, Moscow, 125319, Russian Federation; 3 -The Open Institute of Human and Nature («Atviras Žmogaus Ir Gamtos Institutas»), Laisves pr. 60-1107, Vilnius, LT-05120, Republic of Lithuania

Introduction. Uterine fibroids – a benign tumor, growing from immature muscle cells of the vascular wall of the uterus. It ranked first among the benign tumors of the genital organs, with one in ten suffers from gynecological patients with uterine myoma. The aim of the study. To investigate the involvement of candidate genes combinations in the formation of uterine fibroids. Methods. The sample for the study was 894 people: 394 patients with uterine myoma and 500 women in the control group. Molecular genetic analysis of the locus 10 was carried out by polymerase chain reaction of DNA synthesis using standard oligonucleotide primers and probes. Association of alleles and genotypes studied DNA markers with the formation of uterine fibroids were assessed by analysis of 2×2 contingency tables with calculation of χ2 test with Yates correction for continuity and the odds ratio with 95% confidence intervals. Analysis of the role of genetic variants of combinations of cytokines in the occurrence of uterine fibroids conducted using software APSampler, using the method of Monte Carlo Markov chains and Bayesian nonparametric statistics. Results. There were established associations of genetic polymorphisms of tumor necrosis factor-α (rs1800629 TNFα), Lymphotoxin-α (rs909253 Ltα), factor regulating activation normal T-cell expressed and secreted (rs2107538 RANTES), macrophage inflammatory protein-1 (rs1719153 MIP1β), monocyte chemoattractant – 1 (MCP-1 rs2857657), factor-1, produced by stromal cells (rs1801157 SDF-1), interleukin-1β (IL-1β c.-598 T> C (rs16944)), interleukin-1α (IL-1α c.-949 C> T (rs1800587)), interleukin-4 (IL-4 c.-589 C>T (rs2243250)), interleukin-5 (IL-5 c.-746 T> C (rs2069812)), and combinations thereof with the formation of proliferative diseases of the uterus in females residing in the Central region of Russia. Conclusion. The results demonstrated the involvement of candidate genes and cytokine combinations in the development of uterine fibroids.
Keywords: 
uterine fibroids, cytokines, polymorphism
Список литературы: 
  1. Gornall A.S., Naftalin N.J., Brown L.J.R., Konje J.C. Massive necrosis of cervical ectopic decidua presenting in labour.BJOG: An International Journal of Obstetrics and Gynaecology. 2000; 107 (4): 573–5.
  2. Parker W.H. Uterine myomas: management. Fertility and sterility. 2007; 88 (2): 255–71.
  3. Wang T., Rohan T.E., Gunter M.J., Xue X., Wactawski–Wende J., Rajpathak, S.N. A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. Cancer Epidemiology Biomarkers & Prevention. 2011; 20 (5): 971–7.
  4. Altuchova O.B., Demakova N.A., Pachomov S.P., Batlutskaya I.V. Genetic variations of interleukins are associated with hysteromyoma developing. Res. J. Pharm. Biol. Chem. SCI. 2014; 5 (5): 1065–8.
  5. Churnosov M.I., Altuchova O.B., Demakova N.A., Evdokimov V.I., Sorokina I.N. Analysis of Involvement of cytokine genetic polymorphisms in development of genital endometriosis. Res. J. Pharm. Biol. Chem. SCI. 2014; 5 (5): 1027–31.
  6. Sosna O., Kolesar L., Slavcev A., Skibova J., Fait T., Mara M., Kuzel D. Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid Folia Biol. 2010; 56 (5): 206–10.
  7. Taghizade–Mortezaee F., Hashemzadeh– Chaleshtori M., Kheiri S., Parvin N., Norbakhsh M., Etemadi S., Mirj S. Association of Interleukin-1β (IL-1β) Gene Polymorphisms with Uterine Leiomyoma. Zahedan J. of Research in Med. Sciences. 2012; 14 (7): 53–6.
  8. Khorasani M.M., Salimi S., Hajizade A., Moossavi M., Tabatabai E., Yaghmaei M., Mashhadi F.F. Lack of Association Between IL-1 Receptor Antagonist Gene 86bp VNTR Polymorphism and Uterine Leiomyoma. Gene Cell Tissue. 2014; 1 (1): 5.
  9. Trevilatto P.C., ScarelCaminaga R.M., De Brito R.B., De Souza A.P., Line S.R. Polymorphism at position – 174 of IL-6 gene is associated with susceptibility to chronic periodontitis in a Caucasian Brazilian population. J. of Clin. Periodontology. 2003; 30 (5): 438–42.
  10. Landi S., Moreno V., Gioia–Patricola L., Guino E., Navarro M., de Oca J., Canzian F. Association of common polymorphisms in inflammatory genes interleukin (IL) 6, IL8, tumor necrosis factor α, NFKB1, and peroxisome proliferatoractivated receptor γ with colorectal cancer. Cancer research. 2003; 63 (13): 3560–6.
  11. Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research. 1988; 16 (3): 1215.
  12. Favorov A.V., Andreewski T.V., Sudomoina M.A., Favorova O.O., Parmigiani G., Ochs M.F. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans. Genetics. 2005; 171 (4): 2113–21.
  13. Hutyrova B., Pantelidis P., Drabek J., Zurkova M., Kolek V., Lenhart K., Petrek M. Interleukin-1 gene cluster polymorphisms in sarcoidosis and idiopathic pulmonary fibrosis. Am. J. of respiratory and critical care med. 2002; 165 (2): 148–51.
  14. Bodienkova G.M., Titova Zh.V. Rol` poli morfizma i e`kspressii genov citokinov v formirovanii patologii (Obzor). Uspehi sovremennogo estestvoznaniya. 2015; 1–4. [Bodienkova G.M., Titova ZH.V. Rol’ polimorfizma i ehkspressii genov citokinov v formirovaniipatologi (Obzor). Uspekhi sovremennogo estestvoznaniya. 2015; 1–4 (in Russian)]
  15. Chae S.J., Kim H., Jee B.C. Tumor necrosis factor (TNF)-TNF receptor gene polymorphisms and their serum levels in Korean women with endometriosis. Am. J. Reprod. Immunol. 2008; (5): 432–9.