Combination of gene forms of phases I and II of the xenobiotic biotransformation system and the risk of pregnancy disorders in women living in a large industrial city

Introduction. 90% of the Kuzbass population lives in an industrial zone with a high level of anthropogenic load. Novokuznetsk is classified as a city with a critically high level of environmental pollution and the risk of developing diseases. The incidence of congenital malformations in the Kemerovo region is on average 3–5 times higher than in the Russian Federation.

Materials and methods. The average annual concentrations of pollutants in the Novokuznetsk urban district for 2020–2022 were calculated. A survey of sixty young primigravida women living in Novokuznetsk was conducted. In more than 50% of cases, gestational sac death was diagnosed. Variants of the CYP1A2 and GSTM1 genes of the xenobiotic biotransformation system were determined in these women by polymerase chain reaction, and their combinations were considered.

Results. A significant excess of the maximum permissible concentrations of benz(a)pyrene, formaldehyde, suspended substances, and nitrogen dioxide was revealed while reducing the total volumes of pollutant emissions into the atmosphere of Novokuznetsk. There was a five-fold increase in the share of congenital malformations and a twenty-fold gain in the number of missed miscarriages over the past 20 years. A statistically reliable association of gestational sac death was found in women with the C/ACYP1A2*1F genotype in combination with a deletion polymorphism of the GSTM1 gene (χ² = 3.94; OR = 7.00), while the C/ACYP1A2*1F genotype in combination with the normally functioning GSTM1 ”+” gene is associated with the resistance to miscarriage (χ² = 9.16; OR = 0.19).

Limitations. The study was of a pilot nature, so it is advisable to increase the sample in the future.

Conclusion. There have been identified combinations of gene forms of phases I and II of the xenobiotic biotransformation system associated with unfavourable pregnancy outcomes which can be used as markers of reproductive losses and taken into account when planning and carrying a pregnancy.

Compliance with ethical standards. The examination of patients corresponded to the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, elaborated in accordance with the Declaration of Helsinki of the World Medical “Ethical Principles for Medical Research Involving Human Subjects” as amended 2013 and the “Rules of Proper Clinical Practice” approved by Order of the Ministry of Health of the Russian Federation dated April 1, 2016 N 200n. Each participant of the study gave informed voluntary written consent to take part in the study.

Contribution:
Gulyaeva O.N. – the concept and design of the study, collection and processing of material, statistical processing, editing;
Kislitsyna V.V. – collection and processing of material;
Zhukova A.G. – the concept of the study, editing;
Kazitskaya A.S. – collection and processing of material;
Yadykina T.K. – collection and processing of material;
Matoshin S.V. – collection and processing of material;
Shramko S.V. – the concept and design of the study.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: May 2, 2024 / Accepted: June 19, 2024 / Published: July 31, 2024