Grant Number:
Principal Investigator:
Wright, Robert O
Institution:
Brigham and Women's Hospital
Most Recent Award Year:
2006
Lifestage of Participants:
Exposure:
Prenatal; Adulthood (mother)
Assessment:
Youth (1-18 years)
Exposures:
Metals:
Arsenic; Lead; Manganese
Mixtures:
Health Outcomes:
Neurological/Cognitive Outcomes:
Neurodevelopmental outcomes
Biological Sample:
Blood (mother, child); Cord blood
Other Participant Data:
Behavioral/Cognitive tests
Genes or Other DNA Products Studied:
Iron metabolism gene variants (e.g., HFE, Transferrin, Transferrin receptor, Divalent metal transport protein-1, GST-M1, T1, and P1)
Abstract:
The developing central nervous system is particularly vulnerable to environmental toxicants. While lead poisoning has been extensively studied and public health measures to reduce exposure implemented, exposure is still high in some populations. Other toxic metals (arsenic and manganese for example) remain elevated in the environment, and the effects of arsenic and manganese on neurodevelopment remain poorly understood. Critical questions also remain regarding individual differences in susceptibility to metals (even lead) and whether combinations of neurotoxicants are synergistically toxic. Given this, the effect of joint exposure to combinations of metals is a critical public health issue, as this exposure scenario is more reflective of the real world situation. The role of iron metabolism genes, which may regulate the metabolism of multiple neurotoxic metals, may also play a key role in understanding the mechanisms by which metal mixtures produce neurotoxicity. In this project we will establish a new birth cohort in Mexico City to measure biomarkers of internal dose for manganese, arsenic and lead and analyze their interactions in predicting associations between metal exposure and neurodevelopment. Furthermore, we will study the modifying effects of iron metabolism gene variants (HFE, Transferrin, Transferrin Receptor, and Divalent Metal Transport Protein-1) on the neurotoxicity of these metals and their influence on placental transfer of metals. We will also explore the effect of variants in the GST-M1, T1 and P1 genes on Arsenic neurotoxicity. Our research team is particularly well situated to conduct this work as we have a long-standing collaboration with the National Institute of Public Health in Mexico, enabling us to quickly assemble highly skilled field teams for sample collection and phenotyping. Furthermore, our pilot data suggest that exposure to Mn, As and Pb are elevated in the target population, and that biomarkers of internal dose may be associated with poorer developmental outcomes.
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Related NIEHS-Funded Study Populations
Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT)
Principal Investigator:
Hu, Howard; Peterson, Karen; Hernandez-Avila, Mauricio; Tellez-Rojo, Martha Maria
| Study Population Page Study Population c49
Institution:
University of Michigan
Location:
Mexico City, Mexico
Number of Participants::
1,653
Brief Description::
This is a group of three sequentially-enrolled, on-going, epidemiologic birth cohort studies in Mexico City with an original aim to investigate the impact of lead on child development. The research aims have since expanded to include a wide range health outcomes and environmental, nutritional, behavioral, genetic, and epigenetic risk factors. More than 1,600 mother-child pairs enrolled in the study beginning in 1994, some of whom have been followed for over two decades.