Polymorphism of genes controlling phase I and II detoxification in phenol-exposed women with spontaneous miscarriage diagnosis

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Abstract

The environmental issues in contemporary megapolis require studying of multiple candidate genes that may contribute to occurrence of reproductive disorders. Exogenous phenol compounds are contaminants that produce negative effects upon female reproductive system. Detoxification genes from CYP450 and GSTs family belong to the I and II detoxification phases of xenobiotics including phenols. Our goal was to examine some features of polymorphism in I and II phase detoxication genes in women with diagnosed miscarriage who were subjected to excessive phenol exposure. The test group consisted of 37 women who had miscarriage; the reference group included 41 conditionally healthy women. All the examined women lived under airborn exposure to phenol (an average of > 1.0 daily minimal acceptable concentration). The following parameters were examined in both groups: phenol contents in blood were detected with capillary gas chromatography; polymorphisms of CYP1A1 rs1048943 Ile462Val, CYP1A1_3 rs4646421 C6310T, GSTA4 rs3756980 T/C, GSTP1 rs1695 Ile105Val, GSTP1 rs1138272, and Ala114Val genes were revealed with polymerase chain reaction. There were significant discrepancies between the examined groups, both for phenol contents in blood, compared to upper standardized limits (p < 0.05). The examined gene polymorphisms fit the Hardy–Weinberg rule. Statistical analysis in multiplicative inheritance model allowed us to show that A allele in CYP1A1 rs1048943 Ile462Val gene, and A allele in GSTP1 rs1695 Ile105Val gene could be the factors associated with probable miscarriage risk in case of excessive contamination of biological media with exogenous estrogens (e.g., phenol). The examined gene polymorphisms may be suggested as marker genes for early prediction of miscarriage risk, when excessive contents of exogenous estrogen imitator (phenol) are present in biological media.

About the authors

O. A. Kazakova

Federal Research Center for Medical and Preventive Health Risk Management Technologies

Author for correspondence.
Email: chakina2011@yandex.ru
ORCID iD: 0000-0002-0114-3930

Kazakova Olga A., Junior Research Associate, Laboratory of Immunogenetics

614045, Perm, Monastyrskaya str., 82

Russian Federation

O. V. Dolgikh

Federal Research Center for Medical and Preventive Health Risk Management Technologies

Email: oleg@farisk.ru
ORCID iD: 0000-0003-4860-3145

PhD, MD (Medicine), Professor, Head, Department of Immunological Methods of Diagnostics

Perm

Russian Federation

References

  1. Бабанов С.А., Агаркова И.А., Липатов И.С., Тезиков Ю.В. Профессиональные поражения репродуктивной системы // Гинекология, 2013. № 17. С. 917-920.
  2. Балабанова Л.А. Экологические и профессиональные факторы в генезе репродуктивных нарушений // Практическая медицина, 2008. № 30. С. 16.
  3. Беспалова О.Н., Иващенко Т.Э., Тарасенко О.А., Малышева О.В., Баранов В.С., Айламазян Э.К. Плацентарная недостаточность и полиморфизм генов глютатион-S-трансфераз М1, Т1 и Р1 // Журнал акушерства и женских болезней, 2006. Т. LV, № 2. С. 25-31.
  4. Борисов В.В. Причины растройств и перспективы улучшение репродуктивного здоровья населения России. Клиническая лекция // Consilium medicum, 2017. Т. 19, № 7. С. 70-75.
  5. Викторова Т.В., Исхакова Г.М. Ассоциация полиморфных вариантов генов глутатион зависимых ферментов с репродуктивной патологией у женщин // Проблемы репродукции, 2010. № 4. С. 16-19.
  6. Гордеева Л.А., Воронина Е.Н., Глушков А.Н. Генетические особенности метаболизма ксенобиотиков и предрасположенность к патологии беременности. Часть II // Медицина в Кузбассе, 2016. Т. 15, № 3. С. 3-10.
  7. Казакова О.А., Долгих О.В., Синицина О.О. Иммунный и генетический статус женщин с нарушениями репродуктивной сферы при контаминации биосред фенолом // Гигиена и санитария, 2020. Т. 99, № 1. С. 90-96.
  8. Кублинский К.С. Аллельный полиморфизм генов CYP1A1, CYP1A2, SULT1A1 и SULT1E1 при генитальном эндометриозе // В мире научных открытий, 2016. № 1 (173). С. 36-52.
  9. Носкова И.Н., Артымук Н.В., Масенко Я.Л. Медицинские и социальные аспекты неблагоприятного исхода беременности у женщин сельской местности // Медицина в Кузбассе, 2008. № 1. С. 65-67.
  10. Парагульгова Ф.М., Соснова Е.А. Генетические полиморфизмы факторов, влияющих на фертильность, их роль в привычной потере беременности // Проблемы женского здоровья, 2011. Т. 6, № 3. С. 60-64.
  11. Ehlting J., Hamberger B., Million-Rousseau R., Werck D. Cytochromes P450 in phenolic metabolism. Phytochem.Rev., 2006, Vol. 5, no. 2, pp. 239-270.
  12. Gear R.B., Belcher S.M. Impacts of bisphenol A and ethinyl estradiol on male and female CD 1 mouse spleen. Sci. Rep., 2017, Vol. 7, no. 1, 856. doi: 10.1038/s41598-017-00961-8.
  13. Guneidy R.A., Meguid N.A., Abdel Ghany S.S., Saleh N.S.M., Zaki E.R., Hamed R.R. Inter individual variation of normal and Down syndrome glutathione transferase in response to different phenolic compounds. Res. J. Pharm., Biol. Chem. Sci., 2017, Vol. 8, no. 4, pp. 184-201.
  14. Lee H.S., Yang M. Application of CYP 450 expression for biomonitoring in environmental health. Environ Health Prev. Med., 2008, Vol. 13, pp. 84-93.
  15. Li J., Chen Y., Mo S., Nai D. Potential positive association between cytochrome P450 1A1 gene polymorphisms and recurrent pregnancy loss: a meta analysis. Ann. Hum. Genet., 2017, Vol. 81, no. 4, pp.161-173.
  16. Mortezaee F.T., Chaleshtori M.H., Tabatabaiefar M.A. Lack of association between ESR1 and CYP1A1 gene polymorphisms and susceptibility to uterine leiomyoma in female patients of iranian descent. Cell J., 2014, Vol. 16, no. 2, pp. 225-230.
  17. Niwa T., Murayama N., Imagawa Y., Yamazaki H. Regioselective hydroxylation of steroid hormones by human cytochromes P450. Drug Metab. Rev., 2015, Vol. 47, no. 2, pp. 89-110.
  18. Suryanarayana V., Deenadayal M., Singh L. Association of CYP1A1 gene polymorphism with recurrent pregnancy loss in the South Indian population. Hum. Reprod., 2004, Vol. 19, no. 11, pp. 2648-2652.
  19. Zong C., Sha Y., Xiang H., Wang J., Chen D., Liu J., Wang B., Cao Y. Glutathione S transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population. J. Assist. Reprod. Genet., 2014, Vol. 31, pp. 379-382.
  20. Zusterzeel P.L., Nelen W.L., H.M., Roelofs H.M., Peters W.H., Blom H.J., Steegers E.A. Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss. Mol. Hum. Reprod., 2000, Vol. 6, no. 5, pp. 474-478.

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Copyright (c) 2021 Kazakova O.A., Dolgikh O.V.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
Свидетельство о регистрации СМИ ПИ № 77 - 11525 от 04.01.2002 выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


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