title: Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.
abstract: Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ru-Lan
authors.initials: RL
authors.lastname: Hsieh
authors.affiliation: Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan; School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Tien
authors.initials: CT
authors.lastname: Su
authors.affiliation: Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Horng-Sheng
authors.initials: HS
authors.lastname: Shiue
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiau-Rung
authors.initials: SR
authors.lastname: Huang
authors.affiliation: Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Ming-I
authors.initials: MI
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Mu
authors.affiliation: Department of Digestive Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ymhsueh@tmu.edu.tw.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
mesh_terms: D001151:Arsenic / Q000378:metabolism* / Q000633:toxicity; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
keywords: Arsenic; Arsenic methylation capacity; Arsenic methyltransferase; Developmental delays; Polymorphism