Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India.
MAMTA Health Institute for Mother and Child, New Delhi, India.
PLoS One. 2021 Dec 2;16(12):e0260860. doi: 10.1371/journal.pone.0260860. eCollection 2021.
Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15μM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation.
We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively.
Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04].
High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.
人为空气污染与 DNA 甲基化的异常变化和同型半胱氨酸升高（>15μM/L）有关。叶酸（<3ng/mL）和维生素 B12（<220pg/mL）缺乏也会通过同型半胱氨酸升高降低全基因组甲基化。尽管 B 族维生素补充剂可以减轻空气污染的表观遗传效应，但在特定人群研究中缺乏这种理解。因此，本研究旨在了解空气污染、同型半胱氨酸和营养缺乏对甲基化的作用。
我们在一个单一的孟德尔人群中，分别对来自低污染区和高污染区的 274 人和 270 人进行了横断面研究，检测了同型半胱氨酸、叶酸、维生素 B12（化学发光法）和全基因组甲基化（比色 ELISA 测定法）。在低污染区和高污染区，分别获得了 254 个和 258 个样本的全基因组甲基化结果。
空气污染导致全基因组甲基化中位数显著下降[高污染区：0.84（0.37-1.97）与低污染区：0.96（0.45-2.75），p=0.01]。高同型半胱氨酸与空气污染相结合显著降低了全基因组甲基化[高污染区：0.71（0.34-1.90）与低污染区：0.93（0.45-3.00），p=0.003]。高污染区叶酸缺乏的个体[高污染区：0.70（0.37-1.29）与低污染区：1.21（0.45-3.65）]，全基因组甲基化水平显著降低（p=0.007）。在低污染区，尽管叶酸缺乏，但如果维持正常的维生素 B12 水平，全基因组 DNA 甲基化水平显著提高[2.03（0.60-5.24），p=0.007]。相反，在高污染区，尽管维生素 B12 缺乏，如果维持正常的叶酸状态，全基因组 DNA 甲基化状态会显著改善[0.91（0.36-1.63）]，与维生素 B12 正常个体相比[0.54（0.26-1.13），p=0.04]。
高同型半胱氨酸可能会加重空气污染对 DNA 甲基化的影响。维生素 B12 在低污染区和叶酸在高污染区可能是全基因组甲基化水平变化的重要决定因素。空气污染对甲基化水平的影响可以通过包括饮食或补充 B 族维生素来降低。这可能是在自然环境中采取的公共层面的方法，以防止社区层面的代谢不良。
