Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation.
Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation.
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DOI：
10.1016/j.envint.2013.10.018
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发表时间：
2014-02
影响因子：
11.8
通讯作者：
Kelsey, Karl T.
中科院分区：
文献类型：
--
作者：
Watkins, Deborah J.;Wellenius, Gregory A.;Butler, Rondi A.;Bartell, Scott M.;Fletcher, Tony;Kelsey, Karl T.
关键词：
全氟烷基酸（PFAA）是一种持久性的合成化合物，用于许多消费品。全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）与心血管风险因素以及动物和细胞系统中基因表达和DNA甲基化的变化有关。然而，PFAA暴露是否与LINE-1 DNA甲基化（一种潜在的心血管风险标志物）相关仍不清楚。我们试图在一个高度暴露于PFOA的人群中评估血清PFAAs和LINE-1 DNA甲基化之间的横截面关联。我们在685名成年参与者中（47%为男性，平均年龄± SD=42 ± 11岁）测量了两次血清PFAAs，间隔4 - 5年。我们在第二个时间点（随访）测量了外周血白细胞中LINE-1 DNA甲基化的百分比，并估计了与平均PFAA血清水平四分位数（IQR）偏移相关的LINE-1甲基化的绝对差异。平均血清PFOA、PFOS、全氟壬酸（PFNA）和全氟己烷磺酸盐（PFHxS）的IQR增加分别与随访时LINE-1甲基化%的差异为−0.04（p=0.16）、0.20（p=0.001）、0.06（p=0.19）和0.02（p=0.57）相关。我们观察到LINE-1 DNA甲基化在PFOS和PFNA的三分位数中单调增加（两种关联的ptrend=0.02），但在PFOA或PFHxS的三分位数中没有增加（ptrend=0.71和0.44）。总之，血清全氟辛烷磺酸与LINE-1甲基化相关，而血清全氟辛酸、全氟辛烷磺酸xS和全氟萘酸则与之无关。需要进一步的研究来更精确地确定这些化合物是否具有表观遗传活性。
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 ± 11 years). 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.
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影响因子：
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作者：
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通讯作者：
Deininger PL
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