Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans
Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans
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DOI：
10.1016/j.envint.2013.03.008
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发表时间：
2013-07-01
影响因子：
11.8
通讯作者：
Harries, Lorna W.
中科院分区：
文献类型：
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作者：
Fletcher, Tony;Galloway, Tamara S.;Harries, Lorna W.
全氟辛酸（PFOA，“C8”）和全氟辛烷磺酸（PFOS）是环境稳定的化合物，具有工业和消费用途，在人体中半衰期长。人们担心长期接触会对人类健康产生影响，特别是与胆固醇代谢有关。在这里，我们探讨了 PFOA 和 PFOS 暴露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 名通过饮用水接触 PFOS 背景水平和高浓度 PFOA 的个体。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；p 分别为 0.002、0.026 和 0.014）的全血表达水平之间呈负相关。 PFOS 与参与胆固醇动员的转录本呈正相关（NCEH1；p = 0.018），与参与胆固醇转运的转录本呈负相关（NR1H3；p = 0.044）。当单独分析性别时，发现男性（NPC1、ABCG1 和 PPARA；分别为 p = 0.025、0.024 和 0.012）和女性（NR1H2 表达；p = 0.019）中，PFOA 导致参与胆固醇转运的 mRNA 水平降低，而女性中胆固醇动员转录本（NCEH1；p = 0.036）的水平则有所增加。独自一人。 PFOS 与女性胆固醇动员和运输相关基因的表达呈正相关（NCEH1 和 PPARA；p 分别为 0.003 和 0.039），但对男性没有明显影响。这是有关胆固醇代谢相关基因的体内表达与接触 PFOA 或 PFOS 之间关联的第一份报告，表明接触这些化合物可能会促进高胆固醇血症环境，对人类疾病产生更广泛的影响。 (C) 2013 Elsevier Ltd. 保留所有权利。
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. (C) 2013 Elsevier Ltd. All rights reserved.