CYP1A1 (RS4646421) gene polymorphism and peculiarities of immune profile in children under aerogenic exposure to benzo(a)pyrene

Introduction. The benzo(a)pyrene exposure forms the special phenotype of the immune profile in children. The study of immune system features associated with the polymorphism of detoxification genes is relevant in the conditions of health risks linked with environmental pollution.

Materials and methods. There was performed clinical and laboratory examination of four hundred seventy nine children aged of 3–6 years. The observation group consisted of 308 children living in conditions of aerogenic exposure to benzo(a)pyrene. The comparison group included 171 children from a relatively clean territory. Determination of benzo(a)pyrene concentration in an atmospheric air and in blood was carried out by HPLC. The study of polymorphism of CYP1A1 (rs4646421) gene was carried out by real-time PCR. CD3⁺CD4⁺-lymphocyte phenotyping was performed by flow cytometry, IgG to benzo(a)pyrene — by allergosorbent testing.

Results. Aerogenic exposure to benzo(a)pyrene at an average daily dose of 8.76•10^–2 µg/(kg•day) causes an increase in the level of blood contamination with PAH, forms an imbalance of the immune profile (IgG to benzo(a)pyrene hyperproduction, CD3⁺CD4⁺-lymphocyte expression deficiency and CD4⁺/CD8⁺ decrease) associated with T-allele and CT-genotype of the CYP1A1 gene (rs4646421) (OR(CI)=2.35–6.65; p<0.05). Children with the CT-genotype of the CYP1A1 gene (rs4646421) are characterized by the most pronounced changes in the immune profile (excess IgG to benzo(a)pyrene; reduction of CD3⁺CD4⁺ and CD4⁺/CD8⁺ against the background of maximum blood contamination with benzo(a)pyrene in relation to other genotypic groups (OR(CI)=1.64–3.08; p<0.05).

Limitations. The limitations are related to the need to increase the sample and verify the results obtained in subsequent observations.

Conclusion. The peculiarities of the immune profile in CT-genotype carriers of the CYP1A1 (rs4646421) gene under the conditions of aerogenic exposure to benzo(a)pyrene at a dose of 8.76•10^–2 mcg/(kg•day) should include the formation of specific sensitization to benzo(a)pyrene, deficiency of cellular differentiation clusters: CD3⁺CD4⁺-lymphocytes, CD4⁺/CD8⁺ reduction associated with blood contamination with benzo(a)pyrene, which indicate the likelihood of hereditary predisposition realization and the formation of immune regulation disorders associated with exposure to benzo(a)pyrene.

Compliance with ethical standards. The study was carried out in compliance with the ethical requirements of the Helsinki Declaration of the WMA 2000 and the Protocol of the Council of Europe Convention on Human Rights and Biomedicine 1999. The study was approved by the LEC of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being (Protocol No. 23 of 12/20/2021). Informed consent was obtained for all participants.

Contribution:
Nikonoshina N.A. — genotyping, markers of immune state, statistical processing, writing and editing text;
Dolgikh O.V. — concept and design of research, writing and editing of 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.

Received: October 9, 2023 / Accepted: November 15, 2023 / Published: December 8, 2023