Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women

Xiaoshan Liang; Guanshuai Guo; Yiyun Wang; Meng Wang; Xi Chen; Jingran Zhang; Shuying Li; Liangpo Liu; Qingyu Huang; Bo Cui; Ming Zhang; Guifan Sun; Naijun Tang; Xumei Zhang; Qiang Zhang

doi:10.1016/j.envres.2023.115331

Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women

Environ Res. 2023 Mar 15:221:115331. doi: 10.1016/j.envres.2023.115331. Epub 2023 Jan 19.

Authors

Xiaoshan Liang¹, Guanshuai Guo², Yiyun Wang², Meng Wang³, Xi Chen², Jingran Zhang², Shuying Li⁴, Liangpo Liu⁵, Qingyu Huang⁶, Bo Cui⁷, Ming Zhang⁸, Guifan Sun⁹, Naijun Tang², Xumei Zhang³, Qiang Zhang¹⁰

Affiliations

¹ Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.
² Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.
³ Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.
⁴ Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, 300380, China.
⁵ School of Public Health, Shanxi Medical University, Taiyuan, 030001 China.
⁶ Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China.
⁷ Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Tianjin, 300050, China.
⁸ Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, 518020, China.
⁹ Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang, 110122, China.
¹⁰ Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China. Electronic address: qiangzhang@tmu.edu.cn.

PMID: 36681142
DOI: 10.1016/j.envres.2023.115331

Abstract

Background: Single nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM).

Objective: This study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM.

Methods: A cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism.

Results: Pregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, -0.13) and MMA% (B: 0.21; 95% CI: 0.39, -0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%.

Conclusions: Genetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.

Keywords: AS3MT; Arsenic; Gene-environment interaction; Gestational diabetes mellitus; N6AMT1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arsenic* / metabolism
Cacodylic Acid
Cross-Sectional Studies
Diabetes, Gestational* / genetics
East Asian People
Female
Humans
Methyltransferases / genetics
Methyltransferases / metabolism
Polymorphism, Single Nucleotide
Pregnancy
Pregnant Women
Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics
Site-Specific DNA-Methyltransferase (Adenine-Specific) / metabolism

Substances

Arsenic
Methyltransferases
monomethylarsonic acid
Cacodylic Acid
AS3MT protein, human
N6AMT1 protein, human
Site-Specific DNA-Methyltransferase (Adenine-Specific)