Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

Ru Lan Hsieh, Chien Tien Su, Horng Sheng Shiue, Wei Jen Chen, Shiau Rung Huang, Ying Chin Lin, Ming I. Lin, Shu Chi Mu, Ray Jade Chen, Yu Mei Hsueh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalToxicology and Applied Pharmacology
Volume321
DOIs
Publication statusPublished - Apr 15 2017

Fingerprint

Methylation
Arsenic
Preschool Children
Polymorphism
Taiwan
Metabolism
Genes
Purine-Nucleoside Phosphorylase
Haplotypes
Glutathione Transferase
Genotype
Cacodylic Acid
Atomic absorption spectrometry
Methyltransferases
High performance liquid chromatography
Hydrides
Teaching Hospitals
Gold
Case-Control Studies
Spectrum Analysis

Keywords

  • Arsenic
  • Arsenic methylation capacity
  • Arsenic methyltransferase
  • Developmental delays
  • Polymorphism

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan. / Hsieh, Ru Lan; Su, Chien Tien; Shiue, Horng Sheng; Chen, Wei Jen; Huang, Shiau Rung; Lin, Ying Chin; Lin, Ming I.; Mu, Shu Chi; Chen, Ray Jade; Hsueh, Yu Mei.

In: Toxicology and Applied Pharmacology, Vol. 321, 15.04.2017, p. 37-47.

Research output: Contribution to journalArticle

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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.",
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AU - Lin, Ying Chin

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