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Thyroid/parathyroid function and fluoride: role of mitochondrial DNA and SOD genetic variations.
| Journal of Endocrinological Investigation | Sun Q, Feng Z, Sun L, Li C, Wang G, Niu S, Wang Y, Wan H, Huang H, Zhu J, Yu F, Zhou G, Ba Y. |
Children China mitochondrial dysfunction Sex-related difference SOD Oxidative Stress Parathyroid Gland Thyroid Gland Urine-F Human Study

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s40618-026-02823-5

Emerging evidence indicates excessive fluoride exposure damage thyroid/parathyroid, with oxidative stress and mitochondrial dysfunction as crucial mechanisms. However, epidemiological research on their involvement in fluoride-induced thyroid/parathyroid dysfunction and modification of oxidative stress-related SNPs are insufficient. Therefore, we conducted a cross-sectional study (n = 401) among children aged 7–13 in areas with drinking water fluoride exposure in Tongxu County, Henan Province, China. This study examined the associations between urinary fluoride (UF) levels and thyroid/parathyroid function in children, as well as mediation effect of DNA copy number (mtDNA-CN) and interactions between UF and superoxide dismutase (SOD) SNPs. The population was divided into two groups based on children safety guidance of UF (WS/T 256–2005), with respective UF levels of 0.73 mg/L and 2.21 mg/L. Results revealed that for each 1 mg/L increase in children UF, thyroid volume (Tvol) increased by 0.34 cm3 (95%CI: 0.21, 0.46), parathyroid hormone (PTH) levels decreased by 1.40 ng/L (95%CI: -0.21, 0.17), mtDNA-CN reduced by 0.13 unit (95%CI: -0.22, -0.04). Notably, in girls, the UF-Tvol association was partially mediated by relative mtDNA-CN (mediation proportion = 33.08%). Additionally, the GG genotype carriers of SOD2 rs4880 exhibited a larger Tvol (P = 0.017). The TT carriers of SOD3 rs13306703 exhibited higher PTH levels (P < 0.001). GMDR analysis identified an interaction between SOD2 rs4880, SOD3 rs10370 polymorphisms, and UF on Tvol. These findings linked fluoride exposure to thyroid function change in children. mtDNA-CN partially mediating the UF-Tvol association in girls. Genetic variants in SOD2 and SOD3 may modify the effect of fluoride exposure on thyroid.

Graphical abstract

Highlights

• Fluoride exposure linked to alterations of thyroid function.

• Serum PTH levels decreased with the increase of UF levels.

• mtDNA-CN partially explained fluoride-thyroid volume association in girls.

• SOD2 polymorphisms interacted with UF to modulate thyroid volume.

Data availability

Data will be available from the corresponding author on reasonable request.

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Acknowledgements

We thank all members of Tongxu Center for Disease Prevention and Control for their support. We thank all the children and their legal guardian for their enthusiastic participation into the study. This work was supported by the National Natural Science Foundation of China (81972981 and 82003401). The graphical abstract was created by Figdraw.

Author information

Author notes

  1. Qing Sun and Zichen Feng contributed equally to this work.

Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China

    Qing Sun, Zichen Feng, Chunxiang Li, Guoqing Wang, Shu Niu, Yan Wang, Hedan Wan, Hui Huang, Jingyuan Zhu, Fangfang Yu, Guoyu Zhou & Yue Ba

  2. Department of Endemic Disease, Kaifeng Center for Disease Control and Prevention, Kaifeng, 475000, Henan, China

    Long Sun

Contributions

Qing Sun: Conceptualization; Formal analysis; Methodology; Writing-original draft. Zichen Feng: Conceptualization; Writing – review & editing. Long Sun: Resources; Investigation. Chunxiang Li: Data curation; Writing-review & editing. Guoqing Wang: Data curation; Writing-review & editing. Shu Niu: Data curation; Writing-review & editing. Yan Wang: Writing-review & editing; Validation. Hedan Wan: Data curation; Writing-review & editing. Hui Huang: Writing-review & editing; Conceptualization. Jingyuan Zhu: Writing-review & editing; Conceptualization. Fangfang Yu: Conceptualization; Supervision. Guoyu Zhou: Project administration; Funding acquisition. Yue Ba: Writing-review & editing; Supervision; Funding acquisition; Project administration.

Corresponding author

Correspondence to Yue Ba.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Cite this article

Sun, Q., Feng, Z., Sun, L. et al. Thyroid/parathyroid function and fluoride: role of mitochondrial DNA and SOD genetic variations. J Endocrinol Invest (2026). https://doi.org/10.1007/s40618-026-02823-5