Polymorphism of candidate genes MTNR1B C/G (rs10830963) and TCF7L2 C/T (rs7903146) in children as a risk factor for the development of hepatobiliary system pathology in conditions of contamination of biological media with heavy metals (using lead as an example)

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Abstract

Introduction. Lead impact on health considering likely pathways of its molecular interactions in the body have not been given sufficient attention by researchers.

The aim of this study was to assess polymorphism of the MTNR1B C/G (rs10830963) and TCF7L2 C/T (rs7903146) genes in children as a risk factor of hepatobiliary pathology in case of heavy metal contamination in biological media (exemplified by lead).

Materials and methods. We examined ninety three 3–6 years children (39 children had hepatobiliary pathology and 54 children were considered healthy) who were exposed to low-dose airborne lead (0.1MPLa.d.), the average daily dose being 0.4 · 10–3 µg/kg · day. We estimated frequency of alleles and genotypes of the candidate genes MTNR1B C/G (rs10830963) and TCF7L2-1 C/T (rs7903146) associated with levels of lead contamination in biological media and hepatobiliary pathology.

Results. The children from the observation group were established to have authentically high frequency of the G allele (OR=1.92, CI: 1.04–3.54) and GG genotype (OR=7.80, CI: 1.58–38.51; p<0.05) of the MTNR1B gene, as well as C wild type allele (OR=2.07, CI: 1.02–4.20; p<0.05) and CC genotype (OR=2.42, CI: 1.02–5.70; p<0.05) of the TCF7L2-1 gene, which were risk factors (RR=1.20–1.43) of developing hepatobiliary pathology aggravated by lead contamination in blood.

Limitations. Limited sampling, the need to verify the results in further observations.

Conclusion. The study established children with hepatobiliary pathology who lived under long-term low-dose exposure to airborne lead at the dose of 0.4 · 10–3 µg/kg · day (0.1MPLa.d.) to have elevated lead levels in blood and impaired biorhythms of smooth muscles in the bile duct combined with the risk (RR=1.20–1.43) of developing hepatobiliary pathology in carriers of G allele (OR=1.92, CI: 1.04–3.54; p<0.05) of the MTNR1B gene as well as C wild type allele (OR=2.07, CI: 1.02–4.20; p<0.05) of the TCF7L2-1 gene.

Compliance with ethical standards. The study was conducted in compliance with the principles of the Helsinki Declaration of the BMA and approved by the LEK of the Federal State Budgetary Institution “FNC of Medical and Preventive Technologies for Public Health Risk Management” (Minutes of meeting No. 4 dated 01/17/2022). All participants gave informed voluntary written consent to participate in the study.

Contribution:
Dolgikh O.V. – concept and design of the study, editing the text;
Kazakova O.A. – research design, data processing, text writing;
Luchnikova V.A. – material collection and data processing.
All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

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

Acknowledgement. The study had no sponsorship.

Received: September 23, 2024 / Accepted: November 19, 2024 / Published: December 17, 2024

About the authors

Oleg V. Dolgikh

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: fake@neicon.ru

DSc (Medicine), Head of the Department of Immunobiological Diagnostic Methods of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

Olga A. Kazakova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: fake@neicon.ru

PhD (Medicine), senior researcher of the Immunogenetics laboratory of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

Viktoria A. Luchnikova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Author for correspondence.
Email: bezdenezhka@yandex.ru

Junior researcher at the Laboratory of Immunology and allergology of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: bezdenezhka@yandex.ru

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