Division of Occupational and Environmental Medicine, Lund University, Klinikgatan 21, 221 85 Lund, Sweden.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029-5674, USA.
Neurotoxicology. 2018 Jan;64:103-109. doi: 10.1016/j.neuro.2017.09.003. Epub 2017 Sep 13.
Manganese (Mn) is an essential metal that can become neurotoxic at elevated levels with negative consequences on neurodevelopment. We have evaluated the influence of single nucleotide polymorphisms (SNPs) in Mn transporter genes SLC30A10 and SLC39A8 on Mn concentrations in dentine, a validated biomarker that reflects Mn tissue concentrations early in life.
The study included 195 children with variable environmental Mn exposure. Mn concentrations in dentine representing fetal, early postnatal and early childhood developmental periods were measured using laser ablation-inductively coupled plasma mass spectrometry. SLC30A10 rs12064812 (T/C) and SLC39A8 rs13107325 (C/T) were genotyped by TaqMan real time PCR and SLC30A10 rs1776029 (G/A) by pyrosequencing; and SNPs were analyzed in association with Mn in dentine.
SLC39A8 rs13107325 rare allele (T) carriers had significantly higher Mn concentrations in postnatal dentine (110%, p=0.008). For all SNPs we also observed non-significant associations with Mn concentrations in dentine in opposite directions for fetal and early postnatal periods. Furthermore, there were significant differences in the influence of SLC30A10 rs1776929 genotypes on Mn concentrations in dentine between sexes.
The findings from this study indicate that common SNPs in Mn transporters influence Mn homeostasis in early development and may therefore be important to consider in future studies of early life Mn exposure and health effects. Our results also suggest that the influence of these transporters on Mn regulation may differ by developmental stage, as well as between girls and boys.
锰(Mn)是一种必需的金属元素,在高水平下会变得神经毒性,并对神经发育产生负面影响。我们评估了 Mn 转运体基因 SLC30A10 和 SLC39A8 中的单核苷酸多态性(SNPs)对牙本质中 Mn 浓度的影响,牙本质是一种验证过的生物标志物,可反映生命早期的 Mn 组织浓度。
本研究纳入了 195 名具有不同环境 Mn 暴露的儿童。使用激光烧蚀-电感耦合等离子体质谱法测量牙本质中代表胎儿期、早期新生儿期和儿童早期发育阶段的 Mn 浓度。SLC30A10 rs12064812(T/C)和 SLC39A8 rs13107325(C/T)通过 TaqMan 实时 PCR 进行基因分型,SLC30A10 rs1776029(G/A)通过焦磷酸测序进行基因分型;并分析了 SNPs 与牙本质中 Mn 的相关性。
SLC39A8 rs13107325 稀有等位基因(T)携带者的新生儿牙本质中的 Mn 浓度显著升高(110%,p=0.008)。对于所有 SNPs,我们还观察到在胎儿期和早期新生儿期,Mn 浓度呈相反方向的非显著性关联。此外,SLC30A10 rs1776929 基因型对牙本质中 Mn 浓度的影响在性别之间存在显著差异。
本研究结果表明,Mn 转运体中的常见 SNPs 影响早期发育中的 Mn 动态平衡,因此在未来研究早期生活 Mn 暴露和健康影响时可能需要考虑这些因素。我们的研究结果还表明,这些转运体对 Mn 调节的影响可能因发育阶段以及女孩和男孩而异。