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Author Henn, Birgit Claus ♦ Kim, Jonghan ♦ Wessling-Resnick, Marianne ♦ Téllez-Rojo, Martha ♦ Jayawardene, Innocent ♦ Ettinger, Adrienne S. ♦ Hernández-Avila, Mauricio ♦ Schwartz, Joel ♦ Christiani, David C. ♦ Hu, Howard ♦ Wright, Robert O.
Source Paperity
Content type Text
Publisher BioMed Central
File Format PDF ♦ HTM / HTML
Copyright Year ©2011
Abstract Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe -/- mice displayed a significant reduction in blood manganese compared with Hfe +/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.
Learning Resource Type Article
Publisher Date 2011-11-10
e-ISSN 1476069X
Journal Environmental Health
Issue Number 10