Early Life Exposure In Mexico To Environmental Toxicants Research Articles

The Impact of Maternal MTHFR677 Genotype and Lead Exposure on Infant Genomic DNA Methylation

ISEE-0828 Background and Objective: Previous studies have indicated that genetic variations in methylenetetrahydrofolate reductase (MTHFR), a key regulatory enzyme of the one-carbon metabolic pathway, influence genomic DNA methylation levels. However, little is know about the transgenerational influence of the major variant of MTHFR, C677T, on genomic DNA methylation levels. Our objective was to evaluate the impact of maternal MTHFR C677T genotype on cord blood genomic DNA methylation levels and to determine if this association was influenced by maternal lead exposures. Methods: Our subject population consisted of 97 maternal-infant pairs for which DNA methylation and MTHFR genotype data were available from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Genomic DNA methylation, prenatal lead exposure and MTHFR genotyping were assessed by LINE-1 Pyrosequencing, maternal patella bone lead levels using a spot source 109Cd K-XRF instrument and TaqMan technology, respectively. Results: Maternal MTHFR C677T genotype influenced infant LINE-1 DNA methylation levels (CC = 79.86% ± 0.5; CT = 79.83% ± 0.3; and TT = 78.90% ± 0.36; P for trend = 0.07). Furthermore, once stratified by median maternal patella lead exposure, the association between maternal MTHFR C677T genotype and infant LINE-1 DNA methylation was only apparent among mothers with high lead exposure (CC = 80.0% ± 0.93; CT = 79.32% ± 0.48; and TT = 78.35% ± 0.54; P for trend = 0.09); vs. mothers with low lead exposure (CC = 79.79 ± 0.60; CT = 80.39 ± 0.4; and TT = 79.45 ± 0.47; P for trend = 0.51). No significant associations were found among infants MTHFR C677T genotype and DNA methylation. Conclusion: Data from this study suggest that genetic variants of MTHFR C677T among pregnant women are associated with a decrease in genomic DNA methylation in their offspring. Maternal genotype along with environmental exposures may play a large role in epigenetic programming.

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

ISEE-0805 Background: Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility. The objective of this study was to determine if prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples. Methods: Genomic DNA methylation, as assessed by Alu and LINE-1 methylation via pyrosequencing, was measured on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot source 109Cd K-XRF instrument. Results: An inverse dose-response relationship existed between quartiles of patella and tibia lead and cord LINE-1 methylation (P for trend =0.01) and Alu methylation (P for trend = 0.05), respectively. In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β = −0.027; P = 0.01). No associations were found between cord blood lead and cord genomic DNA methylation. Conclusions: Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden and may influence long-term epigenetic programming and disease susceptibility throughout the life-course.

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

BackgroundFetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility.ObjectiveThis study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples.MethodsWe measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source 109Cd K-shell X-ray fluorescence instrument.ResultsWe found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation.ConclusionsPrenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.