Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

Environmental Health

Research

Innocent Jayawardene¹  Howard Hu²  David C Christiani³  Joel Schwartz³  Birgit Claus Henn³  Adrienne S Ettinger⁴  Robert O Wright⁵  Marianne Wessling-Resnick⁶  Jonghan Kim⁶  Martha María Téllez-Rojo⁷  Mauricio Hernández-Avila⁸ 

[1] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, 06510, New Haven, Connecticut, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Department of Emergency Medicine, Children's Hospital Boston, Boston, MA, USA;Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA;Division of Statistics, Center for Evaluation Research and Surveys, National Institute of Public Health, Cuernavaca, Morelos, Mexico;Ministry of Health, Mexico City, Mexico;

关键词: Iron;    Manganese;    Genes;    Iron metabolism genes;   

DOI  :  10.1186/1476-069X-10-97

 received in 2011-07-21, accepted in 2011-11-10,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundGiven mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism.MethodsArchived 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.ResultsPercentage 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Claus Henn et al; licensee BioMed Central Ltd. 2011