title: PFOA and PFOS are associated with reduced expression of the parathyroid hormone 2 receptor (PTH2R) gene in women.
abstract: Little is known about interactions between environmental and genetic risk factors for osteoarthritis (OA). Genetic factors include variation or mutation in genes involved in parathyroid hormone signalling. Exposure to the endocrine disrupting chemicals perfluoro-octanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) have been suggested as potential environmental contributors, although evidence to support this association is conflicting. Here we test the hypothesis that PFOA and PFOS may alter the mRNA expression of genes in the parathyroid signalling cascade to provide evidence on possible pathways between these chemicals and OA. We measured the relationship between PFOA or PFOS serum levels and the in vivo expression of the Parathyroid hormone 1 and 2 genes (PTH, PTH2), Parathyroid hormone 1 and 2 receptor genes (PTH1R, PTH2R) and the parathyroid hormone-like (PTHLH) gene in peripheral blood from a cross-sectional population study designed to assess the potential health effects of these chemicals. We used multivariate linear regression models and found that PFOA or PFOS was inversely correlated with parathyroid hormone 2 receptor (PTH2R) expression (coefficients=-0.43 and -0.32, p=p=0.017 and 0.006 for PFOA and PFOS respectively) in 189 female subjects. The levels of PTH2 transcripts encoding the ligand of PTH2r, were also found to be lower in women with OA (median 2.08) compared with controls (median 3.41, p=0.046). As the parathyroid signalling cascade is a known candidate for osteoarthritis risk and our findings raise the possibility that exposure to these chemicals may contribute to the pathogenesis of OA in some individuals.
authors.affiliation: Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK.
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Galloway
authors.affiliation: Department of Social and Environmental Research, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Fletcher
authors.affiliation: Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Thomas
authors.affiliation: Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Ben P
authors.initials: BP
authors.lastname: Lee
authors.affiliation: Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pilling
authors.affiliation: Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, UK. Electronic address: L.W.Harries@exeter.ac.uk.
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
mesh_terms: D000328:Adult; D017738:Alkanesulfonic Acids / Q000097:blood*; D002210:Caprylates / Q000097:blood*; D003430:Cross-Sectional Studies; D052244:Endocrine Disruptors / Q000097:blood*; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D005466:Fluorocarbons / Q000097:blood*; D015870:Gene Expression; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics; D044183:Receptor, Parathyroid Hormone, Type 2 / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; C473449:PTH1R protein, human; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D044183:Receptor, Parathyroid Hormone, Type 2; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: Gene environment interaction; Human; Osteoarthritis; PFOA; PFOS; PTH2R