Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, RI, USA.
Program in Public Health, University of California, Irvine, CA, USA.
Environ Int. 2014 Feb;63:71-6. doi: 10.1016/j.envint.2013.10.018. Epub 2013 Nov 18.
Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age±SD=42±11years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of -0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active.
全氟烷基酸（PFAAs）是一类持久性的合成化合物，广泛应用于多种消费产品中。全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）与心血管风险因素有关，也会引起动物和细胞系统中的基因表达和 DNA 甲基化改变。然而，PFAA 暴露是否与 LINE-1 DNA 甲基化有关，LINE-1 DNA 甲基化是心血管风险的一个潜在标志物，这在人类中尚不清楚。我们试图在一个高度暴露于 PFOA 的人群中评估血清 PFAAs 与 LINE-1 DNA 甲基化的横断面关联。我们在 685 名成年参与者（47%为男性，平均年龄±标准差=42±11 岁）中，每四年至五年两次测量血清 PFAAs。我们在第二次时间点（随访）测量外周血白细胞中的 LINE-1 DNA 甲基化百分比，并估计与平均 PFAA 血清水平的四分位距（IQR）变化相关的 LINE-1 甲基化的绝对差异。平均血清 PFOA、PFOS、全氟壬酸（PFNA）和全氟己烷磺酸（PFHxS）的 IQR 增加与随访时 LINE-1 甲基化的差异分别为-0.04（p=0.16）、0.20（p=0.001）、0.06（p=0.19）和 0.02（p=0.57），这些差异在调整潜在混杂因素后仍然存在。我们观察到 PFOS 水平与 LINE-1 DNA 甲基化呈单调递增关系，而 PFOA 和 PFHxS 水平则没有（与这两种关联的趋势 p 值分别为 0.02）。总之，血清 PFOS 与 LINE-1 甲基化有关，而血清 PFOA、PFHxS 和 PFNA 则没有。需要进一步的研究来更准确地确定这些化合物是否具有表观遗传活性。
