砷代谢、N6AMT1 和 AS3MT 单核苷酸多态性及其在中国孕妇妊娠糖尿病中的相互作用。
Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women.
机构信息
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.
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.
出版信息
Environ Res. 2023 Mar 15;221:115331. doi: 10.1016/j.envres.2023.115331. Epub 2023 Jan 19.
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.
背景
N6AMT1 和 AS3MT 中的单核苷酸多态性（SNPs）与砷（As）代谢有关，高效的 As 甲基化能力与糖尿病有关。然而，关于妊娠期糖尿病（GDM）的基因-As 相互作用知之甚少。
目的
本研究旨在探讨 N6AMT1 和 AS3MT SNPs 与 As 代谢对 GDM 的单独和联合作用。
方法
对 385 名中国孕妇（86 名 GDM 和 299 名 Non-GDM）进行了横断面研究。对 N6AMT1（rs1997605 和 rs1003671）和 AS3MT（rs1046778 和 rs11191453）中的四个 SNPs 进行了基因分型。测定了尿无机砷（iAs）、一甲基砷酸（MMA）和二甲基砷酸（DMA），并计算了砷形态百分比（iAs%、MMA%和 DMA%），以评估 As 代谢的效率。
结果
与 GG 基因型的孕妇相比，N6AMT1 rs1997605 AA 基因型的孕妇的 iAs%（B：2.11；95%CI：4.08，-0.13）和 MMA%（B：0.21；95%CI：0.39，-0.04）较低。AS3MT rs1046778 和 rs11191453 的 C 等位基因与 iAs%和 MMA%呈负相关，但与 DMA%呈正相关。较高的尿 MMA%与 GDM 风险降低显著相关（OR：0.54；95%CI：0.30，0.97）。N6AMT1 rs1997605 的 A 等位基因（OR：0.46；95%CI：0.26，0.79）与 GDM 风险降低相关。N6AMT1 rs1997605 GG 基因型与较低的 iAs%（AP：0.50；95%CI：0.01，0.99）或较高的 DMA%（AP：0.52；95%CI：0.04，0.99）之间存在统计学显著的相加交互作用。在 N6AMT1 rs1003671 GG 基因型与较低的 iAs%或较高的 DMA%之间也发现了类似的相加交互作用。
结论
中国孕妇中，N6AMT1 中的遗传变异和高效的 As 代谢（以较低的 iAs%和较高的 DMA%表示）可以协同作用，对 GDM 的发生产生协同影响。
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