Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Arch Toxicol. 2019 Sep;93(9):2535-2544. doi: 10.1007/s00204-019-02540-4. Epub 2019 Aug 31.
Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (As), arsenate (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMA %, low InAs %, and high DMA %). High MMA % significantly increased and high DMA % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.
发育迟缓与学龄前儿童砷甲基化能力不足有关。叶酸和维生素 B12 是重要的营养素，它们在一碳代谢中产生 s-腺苷甲硫氨酸，并为砷甲基化提供甲基。本研究旨在探讨血浆叶酸和维生素 B12 水平是否影响砷甲基化能力，进而与学龄前儿童发育迟缓有关。我们于 2010 年 8 月至 2014 年 3 月期间，在新光吴火狮纪念医院进行了一项病例对照研究，共纳入 178 名发育迟缓儿童和 88 名正常儿童。采用高效液相色谱-氢化物发生原子吸收光谱法测定尿中的砷酸盐（As）、亚砷酸盐（As）、一甲基砷酸（MMA）和二甲基砷酸（DMA）。采用 SimulTRAC-SNB 放射性同位素分析法测定血浆叶酸和维生素 B12 水平。结果表明，高血浆叶酸和高维生素 B12 水平的组合与有效的砷甲基化能力相关（低 MMA%、低 InAs%和高 DMA%）。在低血浆叶酸和低维生素 B12（低/低）组中，高 MMA%显著增加，高 DMA%和二次甲基化指数降低，其发育迟缓的比值比（OR）呈剂量依赖性；多变量 OR 和 95%置信区间分别为 5.01（0.83-30.06）、0.21（0.04-1.23）和 0.20（0.03-1.20）。这是第一项表明高血浆叶酸和高维生素 B12 水平的组合增加砷甲基化能力，并间接降低学龄前儿童发育迟缓 OR 的研究。
