Hemochromatosis Gene Variants Modify Placental Transfer of Lead

Abstract

P-271 Introduction: The hemochromatosis gene (HFE) regulates iron absorption and metabolism. Common variants in this gene have been associated with decreased bone and blood lead levels in adults. HFE genotype effects on umbilical cord lead levels or genotype-specific effects on placental lead transfer have not been reported to our knowledge. Methods: This study was nested within a randomized controlled trial of calcium supplementation in breastfeeding mothers in and around Mexico City. Mothers were recruited during pregnancy and followed longitudinally. Peripheral maternal and infant umbilical cord blood samples were collected at delivery and used to measure lead concentration and for HFE genotyping. Two HFE polymorphisms (C282Y and H63D) were genotyped. Results: Paired data on umbilical cord and maternal blood lead levels were available on 265 mother infant pairs of whom 237 pairs were genotyped. Mean (STD) umbilical cord and maternal blood lead levels were 6.6 (3.6) ug/dL and 8.7(4.1) ug/dL respectively. As expected, maternal blood lead at delivery was strongly predictive of umbilical cord lead (beta=0.7, p<0.0001; R2=0.74). All genotypes were in Hardy-Weinberg Equilibrium. Carriers of either C282Y or H63D were combined into a single variable denoting presence or absence of either variant. Presence of an HFE variant in the mother was associated with a 0.6 ug/dL lower umbilical cord blood lead level (p=0.04) when HFE genotype was entered into the model as an independent predictor, adjusting for maternal blood lead levels. Infant HFE genotype did not predict infant cord blood lead levels when entered as an independent variable. Infant HFE genotype also did not modify the association between maternal and infant blood lead levels at delivery. However, Maternal HFE genotype did modify this association-interaction beta (HFE genotype X maternal blood lead) = −0.3 p<0.0001), such that mothers with HFE variants had infants with lower umbilical cord blood lead levels for a given maternal blood lead level, suggesting that the Maternal HFE variant regulates transplacental lead transfer. Discussion: In this population of urban Mexican children, mothers with at least one copy of an HFE variant allele transferred less lead across the placenta as evidenced by its modification of the association between maternal and umbilical cord lead levels. Our results are consistent with maternal HFE genotype regulating placental lead transfer. In contrast, infant HFE genotype did not modify placental lead transfer.