The degree of anthropogenic load, gene polymorphism of the xenobiotic biotransformation system and congenital malformations as links in the same chain

Introduction. According to epidemiological observations, the level of congenital malformations in children is associated with the degree of chemical pollution of the environment and certain forms of genes of the I and II phases of the xenobiotic biotransformation system.

The study aimed to determine and compare the index of anthropogenic load with the probability of occurrence of congenital malformations of the fetus in combination with gene polymorphisms of I and II phases of the xenobiotic biotransformation system in women living in different administrative territories in the South of Kuzbass.

Material and methods. The level of air pollution in the cities of the South of the Kemerovo region (Kuzbass) was established. Prenatal screening of 1,426 pregnant women at the term of 15-18 weeks in the cities of the South of Kuzbass was carried out. The Real Time-PCR method was used to determine the gene polymorphism of the xenobiotic biotransformation system (CYP1A2, GSTM1) in 53 women of Novokuznetsk who gave birth to newborns with congenital malformations.

Results. In the cities of the South of Kuzbass, with a critical and high degree of pollution of atmospheric air and waterways, many women are at risk of congenital malformations in offsprings. The A/A CYP1A2*1F genotype in combination with the deletion polymorphism of the GSTM1 gene in the mother is reliably associated with the occurrence of congenital malformations in offsprings (χ² — 4.72; р — 0.030; OR — 5.56; CI — 1.05–29.32), and the C/ACYP1A2*1F genotype in combination with the normal functioning GSTM1 “+” gene is associated with resistance to the development of congenital malformations (χ² — 12.53; p — <0.001; OR — 0.11; CI — 0.03–0.4 ). 

Conclusion. Against the background of an increasingly unfavourable ecological situation in Kuzbass and raising the number of newborns with congenital malformations, it is essential to include in the algorithm for early prenatal diagnosis the determination of the forms of genes of different phases of the xenobiotic metabolism system to elaborate an algorithm for reducing the xenobiotic load on the body of pregnant women during critical periods of fetal organogenesis.

Contribution:

Gulyaeva O.N. — the concept and design of the study, collection and processing of material, statistical processing, writing a text, editing;

Zhukova A.G. — editing;

Kazitskaya A.S. — collection and processing of material;

Luzina F.A. — collection and processing of material;

Alekseeva M.V. — collection and processing of material;

Renge L.V. — the concept and design of the study;

Ryabov V.A. — the concept and design of the study, collection and processing of material, statistical processing, writing a text.

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.