title: Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans.
abstract: Perfluorooctanoic acid (PFOA, 'C8') and perfluoroctane sulphonate (PFOS) are environmentally stable compounds with industrial and consumer uses and long half-lives in humans. Concern has been raised over chronic exposure effects to human health, especially in relation to cholesterol metabolism. Here, we explore the association between exposure to PFOA and PFOS and the in vivo expression of genes involved in cholesterol metabolism. We studied 290 individuals exposed to background levels of PFOS and elevated concentrations of PFOA through drinking water. Using adjusted linear regression models, we found inverse associations between serum PFOA levels and the whole blood expression level of genes involved in cholesterol transport (NR1H2, NPC1 and ABCG1; p=0.002, 0.026 and 0.014 respectively). A positive association was seen between PFOS and a transcript involved in cholesterol mobilisation (NCEH1; p=0.018), and a negative relationship with a transcript involved in cholesterol transport (NR1H3; p=0.044). When sexes were analysed separately, reductions in the levels of mRNAs involved in cholesterol transport were seen with PFOA in men (NPC1, ABCG1, and PPARA; p=0.025, 0.024 and 0.012 respectively) and in women (NR1H2 expression; p=0.019), whereas an increase in the levels of a cholesterol mobilisation transcript (NCEH1; p=0.036) was noted in women alone. PFOS was positively associated with expression of genes involved in both cholesterol mobilisation and transport in women (NCEH1 and PPARA; p=0.003 and 0.039 respectively), but no effects were evident in men. This is the first report of associations between the in vivo expression of genes involved in cholesterol metabolism and exposure to PFOA or PFOS, suggested that exposure to these compounds may promote a hypercholesterolaemic environment, with wider implications for human disease.
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.forename: Tamara S
authors.initials: TS
authors.lastname: Galloway
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Paul
authors.initials: P
authors.lastname: Holcroft
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cipelli
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pilling
authors.forename: Debapriya
authors.initials: D
authors.lastname: Mondal
authors.forename: Michael
authors.initials: M
authors.lastname: Luster
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
mesh_terms: D000328:Adult; D002210:Caprylates / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; D002784:Cholesterol