Abstract：
Exposure to fluoride in early childhood has been associated with altered cognition, intelligence, attention, and neurobehavior. Fluoride-related neurodevelopment effects have been shown to vary by sex and very little is known about the mechanistic processes involved. There is limited research on how fluoride exposure impacts the epigenome, potentially leading to changes in DNA methylation of specific genes regulating key developmental processes. In the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride adjusted for specific gravity (CUFsg) concentrations. Whole blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip 850 k Array. In a cross-sectional analysis, we interrogated epigenome-wide DNA methylation at 775,141 CpG loci across the methylome in relation to CUFsg concentrations in 272 early adolescents at age 12 years. Among all participants, higher concentrations of CUF were associated with differential methylation of one CpG (p < 6 × 10-8) located in the gene body of GBF1 (cg25435255). Among females, higher concentrations of CUFsg were associated with differential methylation of 7 CpGs; only three CpGs were differentially methylated among males with no overlap of significant CpGs observed among females. Secondary analyses revealed several differentially methylated regions (DMRs) and CpG loci mapping to genes with key roles in psychiatric outcomes, social interaction, and cognition, as well as immunologic and metabolic phenotypes. While fluoride exposure may impact the epigenome during early adolescence, the functional consequences of these changes are unclear warranting further investigation.
摘要：
儿童早期接触氟化物与认知改变有关，情报,注意,和神经行为。氟化物相关的神经发育作用已被证明因性别而异，并且对所涉及的机制过程知之甚少。关于氟化物暴露如何影响表观基因组的研究有限，可能导致调节关键发育过程的特定基因的DNA甲基化变化。在辛辛那提儿童过敏和空气污染研究（CCAAPS）中，使用微扩散法对尿样进行分析,以确定经比重调整后的儿童尿氟化物(CUFsg)浓度.使用Infinium甲基化EPICBeadChip850k阵列评估全血DNA甲基化。在横截面分析中，我们在272名12岁的早期青少年中调查了整个甲基化组775,141个CpG位点的表观基因组DNA甲基化与CUFsg浓度的关系.在所有参与者中，较高的CUF浓度与位于GBF1（cg25435255）基因体中的一个CpG（p<6×10-8）的差异甲基化有关。在女性中,较高浓度的CUFsg与7个CpG的差异甲基化相关;男性中只有3个CpG差异甲基化,女性中没有观察到显著CpG的重叠.次要分析揭示了几个差异甲基化区域（DMRs）和CpG基因座定位到在精神病结局中具有关键作用的基因。社交互动,和认知，以及免疫和代谢表型。虽然氟化物暴露可能会影响青春期早期的表观基因组，这些变化的功能后果尚不清楚,需要进一步调查.
