Polymorphisms in manganese transporters show developmental stage and sex specific associations with manganese concentrations in primary teeth

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HighlightsFirst study of Mn transporter polymorphisms in relation to early-life Mn in humans.Newly-developed tooth Mn biomarker for monitoring fetal, postnatal and early childhood Mn concentrations.Associations were observed between SLC38A8 SNP and postnatal dentine Mn.The direction of associations differed between sexes and developmental stages.Background: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.Methods: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.Results: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.Discussion: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.

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