Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes

Blanca Sarzo; Reem Abumallouh; Natalia Marín; Sabrina Llop; Andrea Beneito; Inmaculada Lopez-Flores; Nerea Ferrero; Amrit Kaur Sakhi; Ferran Ballester; Maria-Jose Lopez-Espinosa

doi:10.1016/j.envpol.2022.119926

Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes

Environ Pollut. 2022 Oct 15:311:119926. doi: 10.1016/j.envpol.2022.119926. Epub 2022 Aug 11.

Authors

Affiliations

¹ Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain; Department of Microbiology and Ecology, University of Valencia, Valencia, Spain; School of Mathematics, University of Edinburgh, Edinburgh, UK.
² Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
³ Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain.
⁴ Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Electronic address: llop_sab@gva.es.
⁵ Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain.
⁶ Department of Genetics, Faculty of Sciences, University of Granada, Granada, Spain.
⁷ Clinical Chemistry Unit, Public Health Laboratory of Bilbao, Bizcaia, Spain.
⁸ Norwegian Institute of Public Health, Oslo, Norway.
⁹ Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Faculty of Nursing and Chiropody, University of Valencia, Valencia, Spain.

PMID: 35964788
DOI: 10.1016/j.envpol.2022.119926

Abstract

Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation. We studied 387 Spanish mother-neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations. In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: -2.95 [-5.70, -0.11], per twofold phenol increase) - stronger for girls - and less clearly for maternal ethylparaben (EPB) and TSH (-2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4. In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.

Keywords: DIO genes; FT4; Phenols; TSH; TT3; Thyroid hormones.

MeSH terms

Female
Humans
Infant, Newborn
Iodide Peroxidase* / genetics
Iodothyronine Deiodinase Type II
Phenol
Phenols
Pregnancy
Thyroid Hormones
Thyrotropin
Thyroxine*

Substances

Phenols
Thyroid Hormones
Phenol
Thyrotropin
Iodide Peroxidase
Thyroxine