Formaldehyde contamination of biological media and MTHFR A1298C (rs1801131) gene polymorphism as risk factors in the formation of thyroid diseases in children

Introduction. Formaldehyde is a well-known and widespread pollutant, an endocrine disruptor, capable of forming DNA adducts, causing genotoxic stress.

The purpose of the study. To evaluate the contamination of the formaldehyde biosensor and the polymorphism of the MTHFR A1298C gene as risk factors for the formation of thyroid pathology in children.

Materials and methods. Overall, we examined seventy nine adolescents aged of 13.59 ± 1.74 years exposed to airborne formaldehyde at the level of 2.3 average annual MPL; of them, 39 adolescents (the observation group) were diagnosed with other specified disorders of thyroid (E07.8); the reference group was made of 40 conditionally healthy adolescents. We examined levels of specific sensitization to formaldehyde (IgE), chemokine MCP-1, T4, TTH, a/b to TG, a/b to TPO by Elias tests. A1298C polymorphism of the MTHFR gene was estimated by RT PCR.

Results. The level of bioexposure by formaldehyde in the observation group was found to be significantly higher than the background range and in the comparison group by 2.3 and 1.2 times, respectively. Specific immune response was also more prominent in the observation group (1.4 times as high levels of IgE specific to formaldehyde); TTH and MCP-1 levels were also higher in this group, 1.3 and 1.2 times respectively against the reference one. Comparative analysis of A1298C polymorphism of the MTHFR gene revealed authentically higher frequency of the C allele, 1.9 times higher in the observation group against the reference one (OR = 2.55; 95% CI: 1.26–5.16; p < 0,01), and the CC genotype (OR = 19.29; 95% CI: 1.06–350.64; p < 0.01), which creates 1.6 times higher risks of thyroid diseases (RR = 1.58; 95% CI: 1.26–1.95).

Research limitations. The small sample size.

Conclusion. The study findings confirm the hypothesis that additional bioexposure to formaldehyde occurs due to production of endogenous formaldehyde resulting from the A1298C folate cycle modified by the MTHFR gene knock-out. This promotes formation of pathological thyroid phenotype (E07.8).

Compliance with ethical standards. The study was approved by the ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (The Meeting Protocol No. 4 dated February 21, 2023). All participants were informed about the study aim and provided their informed written consent to it.

Contribution of the authors: Dolgikh O.V. — study design, data analysis and interpretation, intermediate approval of the manuscript to be published; Kazakova О.А. — study planning, data analysis and interpretation, creating a draft manuscript; Luchnikova V.А. — participating in creating a draft manuscript. All authors have approved the final version of the article and bear full responsibility for the integrity of all its parts.

Funding. The research was not granted any sponsor support.

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

Received: May 21, 2025 / Accepted: October 8, 2025 / Published: December 17, 2025

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