Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. The authors evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. The blood Mn concentrations were measured by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). In addition, the authors measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort. The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025). The results show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.
Authors: Wahlberg K, Kippler M, Alhamdow A, Rahman SM, Smith DR, Vahter M, Lucchini R, Broberg K. ;Full Source: Toxicological Science. 2015 Dec 1. pii: kfv252. [Epub ahead of print] ;