Association of polymorphism of genes in the xenobiotic biotransformation system with early first pregnancy loss in a large industrial region

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Abstract

Relevance: The 15–20-fold increase in the number of missed miscarriages in Novokuznetsk over the past 25 years amid deteriorating environmental conditions is of great public health concern.

Objective: To conduct a molecular genetic analysis of gene polymorphisms in the xenobiotic metabolism enzyme system, specifically focusing on CYP1A1 (3798 A>G rs4646903), CYP1A2 (-163 A>C, rs762551), GSTM1 (deletion), and GSTT1 (deletion), as potential genetic risk factors for early first pregnancy loss among women living in a large industrial region.

Materials and methods: This case-control study included 358 primigravida women, matched for age, residing in a large industrial region from 2021 to 2023. Among them, 186 had normal births, while 172 had missed miscarriages before the 12th week of gestation. Gene polymorphisms in the xenobiotic biotransformation system (glutathione-S-transferases and cytochrome P450) were examined using venous blood samples from 102 women (53 with normal births and 49 with missed miscarriages).

Results: Women with normal childbirth were significantly more likely to have the AA genotype of CYP1A1 and the normal genotypes of GSTM1 and GSTT1 (p=0.016 and p=0.002, respectively). In contrast, patients with missed miscarriages had the AG genotype of CYP1A1 (p=0.046), the AA genotype of CYP1A2 (p=0.03), and deletion polymorphisms in GSTM1 and GSTT1 (p<0.001 and p=0.004, respectively).

Conclusion: The combination of the AG genotype of CYP1A1 and the AA genotype of CYP1A2, along with deletion polymorphisms in GSTM1 and GSTT1, is associated with an increased risk of miscarriage. The findings of this study can be utilized for biological optimization, career guidance, and the prevention of missed miscarriages among women living in large industrial regions.

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About the authors

Svetlana V. Shramko

Novokuznetsk State Institute of Advanced Medical Training, Branch of Russian Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation

Author for correspondence.
Email: shramko_08@mail.ru
ORCID iD: 0000-0003-1299-165X

Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics and Gynecology

Russian Federation, Novokuznetsk

Sergey V. Matoshin

Novokuznetsk State Institute of Advanced Medical Training, Branch of Russian Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation

Email: matoshin94@bk.ru
ORCID iD: 0000-0002-2805-6829

Obstetrician-Gynecologist, PP Student at the Department of Obstetrics and Gynecology

Russian Federation, Novokuznetsk

Olga N. Gulyaeva

Research Institute for Complex Problems of Hygiene and Occupational Diseases, Ministry of Science and Higher Education of the Russian Federation

Email: Gulyaich1973@mail.ru
ORCID iD: 0000-0003-2225-6923

Senior Researcher at the Laboratory for Molecular-Genetic and Experimental Researches

Russian Federation, Novokuznetsk

Irina V. Samus

Research Institute for Complex Issues of Cardiovascular Diseases, Ministry of Science and Higher Education of the Russian Federation

Email: stat-for-you@yandex.ru
ORCID iD: 0000-0002-3293-5746

PhD, Senior Researcher

Russian Federation, Kemerovo

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