Genetic Determinants of Endometriosis and Uterine Myoma Combinatin

Author Name(s): Irina V. Ponomarenko, Vladimir F. Kulikovskiy, Irina V. Batlutkaya, Alexey V. Polonikov, Mikhail I. Churnosov
Author Email: Ponomarenko_i@bsu.edu.ru

Abstract

Benign proliferative diseases of the uterus, which include uterine myoma and endometriosis occupy a leading place in the structure of gynecological diseases. The objective of the research was a bioinformatic study of the involvement of candidate genes in the formation of a combination of endometriosis with uterine myoma in women. As a result of the study, 5 molecular-genetic markers were genotyped in 109 patients with a combination of endometriosis with uterine myoma and 981 women of the control group. It has been established that the combinations of molecular genetic markers rs466639 with rs713586 and rs10441737 (OR = 2.45) and rs466639 with rs3756261, rs713586 and rs10980926 (OR = 1.36) are risk factors for the development of a combination of endometriosis and uterine myoma among women of the Central region of Russia.

Introduction

The relevance of benign proliferative diseases of the uterus, which include uterine myoma and endometriosis, is associated with a fairly high prevalence and comorbidity of these pathological conditions due to the common etiology and pathogenesis, which explains a similar in most cases clinical pattern.

Endometriosis is a process when benign proliferation of tissue occurs outside the uterine cavity, similar to the endometrium in the morphological and functional properties [Bruner-Tran K.L. et al., 2013]. This disease occurs in 10% of women of reproductive age [Rahmioglu N. et al., 2015] and is one of the main causes of infertility, dysmenorrhea, dyspareunia, as well as chronic pelvic pain, adhesion of the pelvic organs, which together leads to a general deterioration quality of life of women [Truskinovsky A.M. et al., 2014; Ponomarenko I.V. et al., 2016].

Uterine myoma is one of the most common female genital benign tumors that occurs in 20-40% of women of reproductive age [Churnosov M.I. et al., 2014; Taylor D.K. et al., 2015; Pachomov S.P. et al., 2016]. Clinical manifestations of this disease are associated with uterine bleeding, pain, compression of adjacent organs, miscarriage [Commandeur A.E. et al., 2015; Krivoshei I.V. et al., 2015a]. As a consequence, uterine myoma becomes the main cause of hysterectomy in many countries of the world. Benign proliferative diseases of the uterus have a common pathogenesis and therefore often occur concomitantly. Thus, 27% of women with endometriosis have concomitant uterine myoma [Donato N.D. et al., 2014; Krivoshei I.V. et al., 2015 b]. One of the factors predetermining the development of endometriosis and uterine myoma may be the age of menarche and associated candidate genes [Elks C.E. et al., 2010]. The objective of the study was a bioinformatic study of the involvement of candidate genes in the formation of a combination of endometriosis with uterine myoma in women.

Conclusion

Thus, the results of the study allow us to conclude that the combinations of molecular genetic markers rs466639 with rs713586 and rs10441737 (OR = 2.45) and rs466639 with rs3756261, rs713586 and rs10980926 (OR = 1.36) are risk factors for the development of a combination of endometriosis and uterine myoma among women of the Central region of Russia.

 References

  1. Bruner-Tran, L., J.L. Herington, A.J. Duleba, H.S. Taylor, K.G. Osteen, 2013. Medical Management of Endometriosis: Emerging Evidence Linking Inflammation to Disease Pathophysiology. Minerva Ginecol., 65(2):199–213.
  2. Chang, W.-C., -L. Wu,.  W.-C. Huang, 2015. PTX3 gene activation in EGF-induced head and neck cancer cell metastasis. Oncotarget, 6(10): 7741–7757.
  3. Churnosov, M.I., O.B. Altuchova, N.A. Demakova, I.V.Krivoshei, V.I. Evdokimov, I.V. Batlutskaya, A.V. Polonikov, 2014. Associations of Cytokines Genetic Variants with Myomatous Knots Sizes. Research Journal of Pharmaceutical, Biological and Chemical, 5(6): 1344-1347.
  4. Commandeur, A.E., A.K. Styer, J.M. Teixeira, 2015. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Hum Reprod Update, 21(5): 593–615.
  5. Cousminer, D.L., E. Stergiakouli, D.J. Berry, 2014. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Human Molecular Genetics, 23(16): 4452–4464.
  6. Demerath, E.W., C.-T. Liu, N. Franceschini, G. Chen, J.R. Palmer,N. Smith, C.T.L. Chen, C.B. Ambrosone, 2013. Genome-wide association study of age at menarche in African-American women. Hum Mol Genet, 22(16): 3329–3346.
  7. Donato, N.D., R. Seracchioli, 2014. How to Evaluate Adenomyosis in Patients Affected by Endometriosis? Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146361/(accessed 12.08.2014).
  8. Elks, E., J.R.B. Perry, P. Sulem, D.I. Chasman, N. Franceschini, C. He, K.L. Lunetta, 2010. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet, 42(12): 1077–1085.
  9. Favorov, A.V., T.V. Andreewski, M.A. Sudomoina, O.O. Favorova. AFоrmattоЕxchangеGеnе-RеlatеdPrоbabilitiеs. BiоmоlеcularStructurе& Dynamics, 29(2): 417-423.
  10. Krivoshei, I.V., O.B. Altuchova, O.V. Golovchenko, V.S. Orlova, A.V. Polonikov, M.I. Churnosov, 2015 a. Genetic factors of hysteromyoma. Research Journal of Medical Sciences, 9 (4): 182-185.
  11. Krivoshei, I.V., O.B. Altuchova, A.V. Polonikov, M.I. Churnosov, 2015 b. Bioinformatic Analysis of the Liability to the Hyperplastic Processes of the Uterus. Research Journal of Pharmaceutical, Biological and Chemical Sciences, №6(5): 1563-1566.
  12. Lien, G.-S., -S. Wu, M.-Y. Bien, 2014. Epidermal Growth Factor Stimulates Nuclear Factor-κB Activation and Heme Oxygenase-1 Expression via c-Src, NADPH Oxidase, PI3K, and Akt in Human Colon Cancer Cells. PLoS One, 9(8): e104891.
  13. Miller, S. A., Dykes, D. D., Polesky, H. F., 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research, 16(3): 1215.
  14. Pachomov, S.P., I.V. Ponomarenko, V.F. Kulikovskiy, V.S. Orlova, E.N. Krikun, I.N. Sorokina, I.V. Batlutskaya, O.Y. Bushueva, 2016. Analysis of Candidate Genes for Uterine Fibroids. Research Journal of Pharmaceutical, Biological and Chemical Sciences, №7(6): 3239-3242.
  15. Perry, J.R., 2014. Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche. Nature. 2014; 514(7520):92–97.
  16. Ponomarenko, I.V., Altuchova, O.B., Golovchenko, O.V., Sorokina, I.N., Polonikov, A.V., Bushueva, O.Y., and Churnosov, M.I., 2016. Molecular-genetic factors of genital endometriosis. International Journal of Pharmacy and Technology, 8(2): 14190-14195.
  17. Rahmioglu, N., S. Macgregor, A.W. Drong, Å.K. Hedman, H.R. Harris,C. Randall, I. Prokopenko, 2015. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. Hum Mol Genet,24(4): 1185–1199.
  18. Speliotes, E.K., L.M. Yerges-Armstrong, Wu, 2011. Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits. PLoS Genet., 7(3):e1001324.
  19. Taylor, D.K., K. Holthouser, J.H. Segars, 2015. Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management. List., 4: 183.
  20. Truskinovsky, A.M., B. Lifschitz-Mercer, B. Czernobilsky, 2014. Hyperplasia and carcinoma in secretory endometrium: a diagnostic challenge. Gynecological Pathology, 33(2): 107–113.
  21. Yarom, N., D.J. Jonker, The role of the epidermal growth factor receptor in the mechanism and treatment of colorectal cancer. Discov Med., 11(57): 95–105.

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