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Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan

  • Toxicogenomics and Omics Technologies
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Abstract

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography–hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26–0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose–response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

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Acknowledgements

We appreciate the assistance with study subject recruitment provided by Drs. Tseng-Chen Sung, Cheng Hui Lin, and Ling-Jen Wang of the Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital. The present study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (SKH-TMU-102–10, SKH-TMU-100-06, and SKH-TMU-99-03), the National Science Council (NSC 100-2314-B-038 -026, NSC 101-2314-B-038-051-MY3 (1–3), NSC 101-2314-B-038 -051-MY3 (2–3), NSC 101-2314-B-038 -051-MY3 (3–3)), and the Ministry of Science and Technology (MOST103-2314-B-038-021-MY2 (1–2), MOST103-2314-B-038-021-MY2 (2–2), MOST 105-2314-B-038-082, MOST 106-2314-B-038-066, MOST 107-2314-B-038-073, and MOST 108-2314-B-038-089).

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Authors and Affiliations

  1. Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Yu-Mei Hsueh & Ying-Chin Lin

  2. Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yu-Mei Hsueh & Ya-Li Huang

  3. Department of Geriatric Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ying-Chin Lin

  4. Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ying-Chin Lin & Chien-Tien Su

  5. Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

    Chi-Jung Chung

  6. Department of Medical Research, China Medical University and Hospital, Taichung, Taiwan

    Chi-Jung Chung

  7. Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Ru-Lan Hsieh

  8. Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ru-Lan Hsieh

  9. Department of Occupational Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Pai-Tsang Huang

  10. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Mei-Yi Wu

  11. Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

    Mei-Yi Wu

  12. Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Horng-Sheng Shiue

  13. School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan

    Ssu-Ning Chien & Chien-Tien Su

  14. Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

    Chih-Ying Lee

  15. Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Ming-I. Lin & Shu-Chi Mu

  16. Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan

    Chien-Tien Su

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  1. Yu-Mei Hsueh
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Hsueh, YM., Lin, YC., Chung, CJ. et al. Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan. Arch Toxicol 94, 2027–2038 (2020). https://doi.org/10.1007/s00204-020-02745-y

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