title: Association between exposure to organochlorine compounds and maternal thyroid status: Role of the iodothyronine deiodinase 1 gene.
abstract: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action.
  
  
  
  To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes.
  
  
  
  The study population (n=1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003-2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4´-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) were measured in serum samples taken during the first trimester of pregnancy (mean [standard deviation (SD)]: 13.5 [2] weeks of gestation). Polymorphisms in DIO1 (rs2235544) and DIO2 (rs12885300) were genotyped in maternal DNA. Sociodemographic and dietary characteristics were obtained by questionnaire.
  
  
  
  A 2-fold increase in HCB was associated with lower TT3 (% change=-1.48; 95%CI: -2.36, -0.60). Women in the third tertile for b-HCH had lower TT3 (% change=-3.19; 95%CI: -5.64, -0.67). The interactions between DIO1 rs2235544 and PCB153 and b-HCH were statistically significant. The inverse association between PCB153 and TT3 was the strongest among women with AA genotype. Women with CC genotype presented the strongest inverse association between b-HCH and FT4.
  
  
  
  Exposure to HCB and b-HCH was associated to a disruption in maternal TT3. The DIO1 rs2235544 SNP modified the association between exposure to some of the OCs (specifically b-HCH and PCB153) and maternal thyroid hormone levels. These results strengthen the hypothesis that DIO enzymes play a role in explaining the disruption of thyroid hormones in relation to exposure to OCs.
authors.affiliation: Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. Electronic address: llop_sab@gva.es.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Llop
authors.affiliation: Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Murcia
authors.affiliation: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Alvarez-Pedrerol
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDÆA-CSIC), Barcelona, Spain.
authors.forename: Joan O
authors.initials: JO
authors.lastname: Grimalt
authors.affiliation: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Biodonostia, Instituto de Investigación Biomédica, San Sebastián, Spain; Departamento de Sanidad Gobierno Vasco, Subdirección de Salud Pública de Gipuzkoa, San Sebastián, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Santa-Marina
authors.affiliation: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Julvez
authors.affiliation: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Biodonostia, Instituto de Investigación Biomédica, San Sebastián, Spain; Public Health Laboratory, Basque Government, San Sebastian, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Goñi-Irigoyen
authors.affiliation: Public Health Laboratory, Basque Government, Bizkaia, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espada
authors.affiliation: Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Ballester
authors.affiliation: Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Medicine, Universitat Jaume I, Castelló de la Plana, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Rebagliato
authors.affiliation: Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Lopez-Espinosa
mesh_terms: D000328:Adult; D004032:Diet; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood*; D007453:Iodide Peroxidase / Q000235:genetics*; D011247:Pregnancy / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood*; D013030:Spain; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D006843:Hydrocarbons, Chlorinated; D014284:Triiodothyronine; D013972:Thyrotropin; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D013974:Thyroxine
keywords: Deiodinase enzymes; Fetal development; Organochlorine compounds; Pregnancy; Thyroid