Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children

Kaihong Xu; Zichen Feng; Francis Kojo Afrim; Jun Ma; Shuo Yang; Xuanyin Zhang; Zeyuan Niu; Ning An; Yuhui Du; Fangfang Yu; Guoyu Zhou; Yue Ba

doi:10.1016/j.chemosphere.2022.135156

Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children

Chemosphere. 2022 Sep;303(Pt 2):135156. doi: 10.1016/j.chemosphere.2022.135156. Epub 2022 May 28.

Authors

Kaihong Xu¹, Zichen Feng¹, Francis Kojo Afrim¹, Jun Ma², Shuo Yang¹, Xuanyin Zhang¹, Zeyuan Niu¹, Ning An¹, Yuhui Du¹, Fangfang Yu¹, Guoyu Zhou¹, Yue Ba³

Affiliations

¹ Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China.
² Department of Endemic Disease, Kaifeng Center for Disease Control and Prevention, Kaifeng, Henan, 475000, China.
³ Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China. Electronic address: byyue@zzu.edu.cn.

PMID: 35640685
DOI: 10.1016/j.chemosphere.2022.135156

Abstract

Objectives: To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children.

Study design: A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF >1.41 mg/L) and low fluoride exposure group (LFG, CUF ≤1.41 mg/L) according to the median concentration of CUF (1.41 mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models.

Results: Negative and positive associations between serum TT4 level (β = -0.721, 95%CI: -1.209, -0.234) and Tvol (β = 0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P < 0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P < 0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P < 0.05, respectively).

Conclusions: Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

Keywords: CREB1 gene; Children; Fluoride; SNP; Thyroid.

MeSH terms

Child
Creatinine
Cross-Sectional Studies
Cyclic AMP Response Element-Binding Protein
Female
Fluorides* / toxicity
Humans
Male
Polymorphism, Single Nucleotide
Thyroid Gland*
Thyroxine
Triiodothyronine

Substances

CREB1 protein, human
Cyclic AMP Response Element-Binding Protein
Triiodothyronine
Creatinine
Thyroxine
Fluorides