NAT2, GST T1, and GST M1 gene polymorphisms in women with pelvic organ prolapse and stress urinary incontinence

Abstract

The objective. The relationship between C481T(S1), G590A(S2), and G857A(S3) polymorphisms in acetyltransferase 2-coding NAT2 gene and glutathione-S-transferase T1 and M1 deletion polymorphisms in GST T1 (del) and GST M1 (del) genes and the risk of pelvic organ prolapse (POP) and stress urinary incontinence (SIU) was studied. Patients and Methods. The study was carried out in 2 groups of patients. Group 1 consisted of patients with stages I-IV POP according to POP-Q scale (n=67). Group 2 included patients with POP and SIU (n=63). Control group (n=89) included women without POP and complaint of SIU. Specimens of DNA were isolated from whole blood. Polymorphisms were identified by PCR by evaluating the restriction fragment length polymorphisms. Results. Significant differences in the incidence of NAT2, GST T1, GST M1 polymorphisms in the patients and controls were detected. Genotype NAT2 N/N was associated with a 3.7 times lesser probability of POP with SIU (OR=3.67, 95% CI 1.01- 13.38). Genotype GSTM1 (del) was associated with higher probability of POP with SIU - about 1.5 times (OR=1.49, 95% CI 1.04-2.15). Combined genotype GST T1+/GST M1+ was associated with a 2.5 times lower probability of POP with SIU (OR=2.5, 95% CI 1.19-2.24). Conclusion. Hence, NAT2 gene C481T(S1), G590A(S2), and G857A(S3) polymorphisms and GST T1(del) and GS TM1(del) gene deletion polymorphisms were involved in the etiology and pathogenesis of POP and SIU.

Keywords

NAT2 / GSTT1 / GSTM / pelvic organ prolapse / stress urinary incontinence / NAT2 / GST T1 / GST M1

References

[1] Смольнова Т.Ю. Клинико-патогенетические аспекты опущения и выпадения внутренних половых органов и патологии структур тазового комплекса у женщин при дисплазии соединительной ткани. Тактика ведения: Дисс.. М.; 2009.

[2] Баранов В.С. Генетический паспорт - основа индивидуальной и предиктивной медицины. СПб.: Н-Л; 2009.

[3] Апокина А.Н. Прогнозирование эффективности хирургической коррекции пролапса тазовых органов: Дисс.. М.; 2012.

[4] Campeau L., Gorbachinsky I., Badlani G.H., Andersson K.E. Pelvic floor disorders: linking genetic risk factors to biochemical changes. Br. J. Urol. Int. 2011; 108 (8): 1240-7.

[5] Chen H.-Y., Lin W.-Y., Chen Y.-H., Chen W.-C., Tsai F.-J., Tsai C.-H. Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in Taiwanese women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010; 14: 222-4.

[6] Kluivers K.B., Dijkstra J.R., Hendriks J.C., Lince S.L., Vierhout M.E., van Kempen L.C. COL3A12209G>A is a predictor of pelvic organ prolapse. Int. Urogynecol. J. Pelvic. Floor. Dysfunct. 2009; 20 (9): 1113-8.

[7] Охрименко А.А. Антиоксидант Мексидол в патогенетической терапии дисплазии соединительной ткани. Бюллетень экспериментальной биологии и медицины. 2006; 1: 132-5.

[8] Hein D.W., Doll M.A., Fretland A.J., Leff M.A., Webb S.J., Xiao G.H. et al. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer. Epidemiol. Biomarkers Prevent. 2000; 9; 29-42.

[9] Lin S.Y., Tee Y.T., Ng S.C., Chang H., Lin P., Chen G.D. Changes in the extracellular matrix in the anterior vagina of women with or without prolapse. Int. Urogynecol. J. 2007;18 (1): 43-8.

[10] Moalli P.A., Shand S.H., Zyczynski H.M., Gordy S.C., Meyn L.A. Remodeling of vaginal connective tissue in patients with prolapse. Obstet. and Gynecol. 2005; 106 (5, Pt 1): 953-63.

[11] Адамян Л.В., Смольнова Т.Ю., Банин В.В. Роль «тканевого фенотипа» в развитии гинекологических заболеваний. Проблемы репродукции. 2007; 4: 6-11.

[12] Кадурина Т.И., Горбунова В.Н. Дисплазия соединительной ткани: Руководство для врачей. СПб.: ЭЛБИ; 2009.

[13] Лоуренс Д.Р, Бенитт П.Н. Клиническая фармакология. М.: Медицина; 1993.

[14] Cascorbi I., Brockmoller J., Mrozikiewicz P.M., Muller A., Roots I. Arylamine N-acetyltransferase activity in man. Drug Metab. Rev. 1999; 31 (2): 489-502.

[15] Lucero H.A., Kagan H.M. Lysyl oxidase: an oxidative enzyme and effector of cell function. Review. Cell. Mol. Life Sci. 2006; 63: 2304-16.

[16] Ботвин М.А., Побединский Н.М., Ищенко А.И., Ланчинский В.И. Исследование фенотипа ацетилирования у больных миомой матки. Акушерство и гинекология. 1998; 4: 42-3.

[17] Дегтярева Ю.А. Пролапс тазовых органов у женщин: факторы риска, прогнозирование клинического течения заболевания: Дисс.. СПб.; 2010.

[18] Костюк В.А., Потапович А.И. Биорадикалы и биоантиоксиданты. Минск: БГУ; 2004.

[19] Habdous M., Siest G., Herbeth B., Vincent-Viry M., Visvikis S. Glutathione S-transferases genetic polymorphisms and human diseases: overview of epidemiological studies. Ann. Biol. Clin. 2004; 62 (1): 15-24.

[20] Русина Е.И., Беженарь В.Ф., Иващенко Т.Э. Фактор полиморфизмов генов GST T1 (del) (глютатион-S-трансфераза Т1), GST M1 (del) (глютатион-S-трансфераза М1) в патогенезе пролапса тазовых органов. Журнал акушерства и женских болезней. 2011; LX (спецвыпуск): 76.

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