Effect Modification of Levels of Heavy Metals by Hemochromatosis Genotype among Mother-Infant Pairs: The Tar Creek Birth Cohort

Abstract

ISEE-0323 Background and Objective: Exposure to heavy metals during windows of increased susceptibility such as fetal development can cause adverse growth and neurodevelopmental effects. Hemochromatosis (gene = HFE) is the most common form of excess adult onset iron accumulation disease and the presence of its gene variants can potentially modify the levels of other metals. The study objective was to assess potential effect modification of the association between maternal and fetal exposure to manganese (Mn) and lead (Pb) by two variants of the HFE gene (H63D and C282Y). Methods: A birth cohort of mothers (304) and infants (278) residing around the Tar Creek Superfund Site in Oklahoma (USA) was studied. Maternal and umbilical cord blood Mn and Pb were measured at delivery and blood metal levels were examined in linear regression models stratified by genotype. Results: Prevalence of the HFE C282Y and HFE H63D variants among mothers was approximately 13% and 30%, respectively, while 4% carried both variants. The corresponding values for infants were: 11%, 34% and 4%. Maternal blood Mn was a significant predictor of cord blood Mn among infants carrying at least one copy of either the C282Y or H63D allele (N = 113, β = 0.77; 95% CI: 0.40, 1.14) but not among wild-type infants (N = 165, β = 0.26; 95% CI: −10.01, 0.53). Conversely, wild-type mothers (N = 186) had a higher effect of maternal blood on cord blood Mn (β = 0.62; 95% CI: 0.33, 0.92) and Pb (β = 0.68; 95% CI: 0.60, 0.77) versus those with any HFE variant (N = 118) for Mn (β = 0.13; 95% CI, −0.18, 0.43) and Pb (β = 0.37; 95% CI: 0.23, 0.50). These observations did not change significantly after adjusting for maternal age and parity. Conclusion: Among this population of mother-infant pairs, HFE variants modified the association between maternal and cord blood metal levels. Identifying susceptibility factors for increased metal exposure during pregnancy is important for protecting children from potential exposures.