NAT2 GENE POLYMORPHISM AS A PREDICTOR OF FAILURE FOR SURGICAL TREATMENT OF PELVIC ORGAN PROLAPSE: RESULTS OF A PROSPECTIVE COHORT CLINICAL STUDY

Abstract

Background: Pelvic organ prolapse (POP) is the most frequent disease component in the structure of gynecological pathology (from 28 to 38.9%) and its incidence is increasing. Most of the research studies were initiated to develop various kinds of operative treatment for common prolapse cases (POP-Q III−IV); however, a large number of surgical interventions associated with a high percentage of complications and a high rate of relapses confirm the difficulty for problem-solving. In this regard, there is a need to expand ideas about the pathogenesis of the disease and develop approaches to the prediction of recurrence surgical treatment, choosing the correct and timely treatment strategy. Currently, great importance is given to the study of genetic control of connective tissue metabolism. The evidence demonstrated that polymorphism of NAT2 gene results in genetically determined disorders of connective tissue catabolism which increases the possibility of disease development approximately in 2 times. Point mutations in NAT2 lead to the so-called slow-acetylation which determines the predominance of the decay rate of collagen over its synthesis.

Aim: Analyze the significance of NAT2 polymorphism as a predictor for failure of surgical treatment of pelvic organ prolapse.

Materials and methods: The prospective cohort clinical trial enrolled 140 women of the reproductive age (from 28 to 42 y.o.) with symptomatic prolapse (POP-Q Stage II−III) who were examined and received treatment in the period from 2008 to 2014. All patients underwent surgical treatment of POP. The treatment included colpoperineorrhaphy with levatorplasty. In 12.9% of patients who had stress urinary incontinence — in combination with a loop urethropexies transobturatory access (Transobturator Vaginal Tape, TVT-O). Long-term results of treatment effectiveness were assessed in 3−5 years. Results: The findings revealed that the incidence rate of point mutations of NAT2 gene was >2-fold higher in patients with POP included in the ineffective treatment group (61.8%) if compared to the rate registered in the effective treatment group (30.6%).

Conclusions: The obtained data indicate that the presence of point mutations in NAT2 gene is a poor prognostic factor for general types of genital prolapse and a predictor for failure of surgical treatment.

About the authors

Е. D. Dubinskaya

RUDN University

Email: eka-dubinskaya@yandex.ru
ORCID iD: 0000-0002-8311-0381
Moscow Russian Federation

S. N. Коlesnikova

RUDN University

Author for correspondence.
Email: ksnmed@mail.ru
ORCID iD: 0000-0001-9575-0274
Moscow Russian Federation

М. B. Khamoshina

RUDN University

Email: khamoshina@mail.ru
ORCID iD: 0000-0003-1663-5265
Moscow Russian Federation

М. G. Lebedeva

RUDN University

Email: lebedeva1108@rambler.ru
ORCID iD: 0000-0002-7236-9486
Moscow Russian Federation

М. А. Sounov

RUDN University

Email: msoiunov@mail.ru
ORCID iD: 0000-0002-9156-6936
Moscow Russian Federation

I. N. Коstin

RUDN University

Email: bigbee62@mail.ru
ORCID iD: 0000-0002-3108-7044
Moscow Russian Federation

Z. M. Sokhova

RUDN University

Email: zalyasokh@yandex.ru
ORCID iD: 0000-0002-3807-6153
Moscow Russian Federation

References

  1. Русина Е.И. Смешанное и сочетанное с пролапсом тазовых органов недержание мочи у женщин: патогенез, диагностика, лечение: Автореф. дис. … докт. мед. наук. ― СПб.; 2015. ― 40 с. [Rusina EI. Smeshannoe i sochetannoe s prolapsom tazovykh organov nederzhanie mochi u zhenshchin: patogenez, diagnostika, lechenie. [dissertation abstract] St. Petersburg; 2015. 40 p. (In Russ).]
  2. Радзинский В.Е., Шалаев О.Н., Дурандин Ю.М., и др. Опущение и выпадение половых органов. Перинеология. ― М.: РУДН; 2008. ― 256 c. [Radzinskii VE, Shalaev ON, Durandin YuM, et al. Opushchenie i vypadenie polovykh organov. Perineologiya. Moscow: RUDN; 2008. 256 p. (In Russ).]
  3. Колесникова С.Н., Дубинская Е.Д., Бабичева И.А. Влияние ранних форм пролапса тазовых органов на качество жизни женщин репродуктивного возраста // Академический журнал Западной Сибири. — 2016. — Т.12. — №١ — С. 65–67. [Kolesnikova SN, Dubinskaya ED, Babicheva IA. Vliyanie rannikh form prolapsa tazovykh organov na kachestvo zhizni zhenshchin reproduktivnogo vozrasta. Akademicheskii zhurnal Zapadnoi Sibiri. 2016;12(1):65–67. (In Russ).]
  4. Walker GJA, Gunasekera P. Pelvic organ prolapse and incontinence in developing countries: review of prevalence and risk factors. Int Urogynecol J. 2011;22(2):127–135. doi: 10.1007/s00192-010-1215-0.
  5. Дубинская Е.Д., Бабичева И.А., Колесникова С.Н., и др. Клинические особенности и факторы риска ранних форм пролапса тазовых органов // Вопросы гинекологии, акушерства и перинатологии. — 2015. — Т.14. — №6 — С. 5–11. [Dubinskaya ED, Babicheva IA, Kolesnikova SN, et al. Clinical specificities and risk factors of early forms of pelvic organ prolapse. Problems of gynecology, obstetrics, and perinatology. 2015;14(6):5−11. (In Russ).]
  6. Lowenstein E, Moller LA, Laigaard J, Gimbel H. Reoperation for pelvic organ prolapse: a Danish cohort study with 15-20 years’ follow-up. Int Urogynecol J. 2017:6. doi: 10.1007/s00192-017-3395-3.
  7. Costa J, Towobola B, McDowel C, Ashe R. Recurrent pelvic organ prolapse (POP) following traditional vaginal hysterectomy with or without colporrhaphy in an Irish population. Ulster Med J. 2014;83(1):16–21.
  8. fda.gov [Internet]. FDA strengthens requirements for surgical mesh for the transvaginal repair of pelvic organ prolapse to address safety risks [cited 2017 Nov 1]. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm479732.htm.
  9. Dallenbach P. To mesh or not to mesh: a review of pelvic organ reconstructive surgery. Int J Womens Health. 2015;7:331−343. doi: 10.2147/IJWH.S71236.
  10. Pontiroli AE, Cortelazzi D, Morabito A. Female sexual dysfunction and diabetes: a systematic review and meta-analysis. J Sex Med. 2013;10(4):1044–1051. doi: 10.1111/jsm.12065.
  11. Lucero HA, Kagan HM. Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol Life Sci. 2006;63(19–20):2304–2316. doi: 10.1007/s00018-006-6149-9.
  12. Родионова Л.В., Сороковиков В.А. , Кошкарева З.В. Активность ферментных систем и метаболизм соединительной ткани в патогенезе стенозирующего процесса позвоночного канала // Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук. ― 2015. — №1 ― С. 77–83. [Rodionova LV, Soroko-vikov VA, Koschkareva ZV. Enzyme systems activity and connective tissue metabolism as pathogenetic factors of spinal stenosis (literature review). Bull Vost Sib Naucn Sent. 2015;(1):77−83. (In Russ).]
  13. Русина Е.И., Беженарь В.Ф., Иващенко Т.Э., и др. Особенности полиморфизма генов NAT2, GST t1, GST m1 у женщин с пролапсом тазовых органов и стрессовым недержанием мочи // Архив акушерства и гинекологии им. В.Ф. Снегирева. ― 2014. ― Т.1. ― №2 ― С. 36–40. [Rusina EI, Bezhenar VF, Ivashchenko TE, et al. NAT2, GST T1, and GST M1 gene polymorphisms in women with pelvic organ prolapse and stress urinary incontinence. Arkhiv akusherstva i ginekologii im. V.F. Snegireva. 2014;1(2):36−40. (In Russ).]
  14. Баггиш М.С., Каррам М.М. Атлас анатомии таза и гинекологической хирургии. Пер. с англ. Е.Л. Яроцкой. — Лондон; 2009. [Baggish MS, Karram MM. Atlas of pelvic. Anatomy and gynecologic surgery. 2nd ed. Transl from English by E.L. Yarotskaya, L. Adamyan. Moscow: Elsevier Ltd; 2009. 1184 p. (In Russ).]
  15. Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol. 1996;175(1):10−17. doi: 10.1016/S0002-9378(96)70243-0.
  16. Чечнева М.А., Буянов С.Н., Попов А.А., Краснопольская И.В. Ультразвуковая диагностика пролапса гениталий и недержания мочи у женщин / Под общей ред. B.И. Краснопольского. ― M.: МЕДпресс-информ; 2016. ― 136 c. [Chechneva MA, Buyanov SN, Popov AA, Krasnopol’skaya IV. Ul’trazvukovaya diagnostika prolapsa genitalii i nederzhaniya mochi u zhenshchin. Ed by B.I. Krasnopolskii. Moscow: MEDpress-inform; 2016. 136 p. (In Russ).]
  17. Han LY, Wang L, Wang Q, et al. Association between pelvic organ prolapse and stress urinary incontinence with collagen. Exp Ther Med. 2014;7(5):1337–1341. doi: 10.3892/etm.2014.1563.
  18. Neupane R, Sadeghi Z, Fu R, et al. Mutation screen of LOXL1 in patients with female pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 2014;20(6):316–321. doi: 10.1097/Spv.0000000000000108.
  19. Dal Moro F. The role of lysyl oxidase-like 1 and fibulin-5 in the development of atherosclerosis and pelvic organ prolapse. J Biomed Res. 2013;27(3):242. doi: 10.7555/JBR.27.20130045.
  20. Alarab M, Kufaishi H, Lye S, et al. Expression of extracellular matrix-remodeling proteins is altered in vaginal tissue of premenopausal women with severe pelvic organ prolapse. Reprod Sci. 2014;21(6):704–715. doi: 10.1177/1933719113512529.
  21. Norton PA, Allen-Brady K, Wu J, et al. Clinical characteristics of women with familial pelvic floor disorders. Int Urogynecol J. 2015;26(3):401–406. doi: 10.1007/s00192-014-2513-8.
  22. Buchsbaum GM, Duecy EE. Incontinence and pelvic organ prolapse in parous/nulliparous pairs of identical twins. Neurourol Urodyn. 2008;27(6):496–498. doi: 10.1002/nau.20555.
  23. Knoepp LR, McDermott KC, Munoz A, et al. Joint hypermobility, obstetrical outcomes, and pelvic floor disorders. Int Urogynecol J. 2013;24(5):735–740. doi: 10.1007/s00192-012-1913-x.
  24. Derpapas A, Cartwright R, Upadhyaya P, et al. Lack of association of joint hypermobility with urinary incontinence subtypes and pelvic organ prolapse. BJU Int. 2015
  25. Khadzhieva MB, Kamoeva SV, Chumachenko AG, et al. Fibulin;115(4):639–643. doi: 10.1111/bju.12823. -5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse. Maturitas. 2014;78(4):287–292. doi: 10.1016/j.maturitas.2014.05.003.
  26. Allen-Brady K, Norton PA, Farnham JM, et al. Significant linkage evidence for a predisposition gene for pelvic floor disorders on chromosome 9q21. Am J Hum Genet. 2009;84(5):678–682. doi: 10.1016/j.ajhg.2009.04.002.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2017 "Paediatrician" Publishers LLC



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies