Department of Social and Environmental Research, London School of Hygiene and Tropical Medicine, London, UK.
Environ Int. 2013 Jul;57-58:2-10. doi: 10.1016/j.envint.2013.03.008. Epub 2013 Apr 24.
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.
全氟辛酸（PFOA，'C8'）和全氟辛烷磺酸（PFOS）是具有工业和消费用途的环境稳定化合物，在人体内半衰期长。人们对其慢性暴露对人类健康的影响表示担忧，尤其是与胆固醇代谢有关。在这里，我们探讨了接触 PFOA 和 PFOS 与胆固醇代谢相关基因的体内表达之间的关联。我们研究了 290 名个体，他们通过饮用水接触到背景水平的 PFOS 和升高的 PFOA 浓度。使用调整后的线性回归模型，我们发现血清 PFOA 水平与胆固醇转运相关基因（NR1H2、NPC1 和 ABCG1）的全血表达水平呈负相关（p=0.002、0.026 和 0.014）。PFOS 与胆固醇动员相关的转录物（NCEH1）呈正相关（p=0.018），与胆固醇转运相关的转录物（NR1H3）呈负相关（p=0.044）。当按性别分别分析时，在男性中，PFOA 降低了胆固醇转运相关 mRNA 的水平（NPC1、ABCG1 和 PPARA；p=0.025、0.024 和 0.012），而在女性中，NR1H2 表达降低（p=0.019），而胆固醇动员转录物（NCEH1）的水平增加（p=0.036）。PFOS 与女性胆固醇动员和转运相关基因的表达呈正相关（NCEH1 和 PPARA；p=0.003 和 0.039），但在男性中则没有这种影响。这是首次报道胆固醇代谢相关基因的体内表达与 PFOA 或 PFOS 暴露之间的关联，表明接触这些化合物可能会促进高胆固醇血症环境，对人类疾病有更广泛的影响。
