Superfund Research Program
Lead Exposure, Accumulation in Bone, and Cognitive Toxicity among Elderly Men and Women
Project Leader: Howard Hu
Grant Number: P42ES005947
Funding Period: 1995 - 2000
- Project Summary
Final Progress Reports
Project investigators continued to follow the Normative Aging Study (NAS) subjects and continued analyses of data collected on both the NAS and the Nurses Health Study (NHS). Results have demonstrated that bone lead is a significant predictor of the development of hypertension in the NHS subjects. This study demonstrated that drinking water lead levels in the 1970s predict bone lead levels in the 1990s of individuals who drank that water. Additionally, the study of individual and census measured socioeconomic position as determinants of bone lead concentrations in the NAS demonstrated that both individual and geographic indicators of lower socioeconomic position make independent contributions to having higher bone lead levels. Project investigators demonstrated independent influences of lead in bone and blood on urinary lead concentrations. Results also demonstrated that bone lead is associated with higher serum acid.
Most recently, researchers completed a prospective analysis of bone and blood lead in relation to the development of hypertension in the NAS demonstrating that bone lead levels predict the future development of hypertension. Analysis of NAS data demonstrated that the common polymorphism of delta-aminolevulinic acid dehydratase (ALAD) modifies lead levels in cortical bone and the relationship between bone lead levels and blood lead levels. Further analysis demonstrated that this ALAD polymorphism modified the relationship of bone lead to serum uric acid, with an earlier threshold for positive relationship in carriers of the ALAD 2-allelle.
Work on gene-environment interactions and lead has been extended to examine the potential of polymorphisms governing the dynamics of metallothionein-IIA production. In a laboratory-based study, wide inter-individual variation in the induction of metallothionein-IIA mRNA was found in human lymphocytes, but this variation did not correspond with two of the best-known polymorphisms associated with metallothionein-IIA. Further analysis demonstrated that higher levels of bone resorption (as reflected by levels of N-telopeptide of type I collagen in urine) are associated with a steeper bone lead-urinary lead relationship. Also, in work shared by Project 3, researchers have continued to refine the K-x-ray fluorescence technique and have demonstrated the close correspondence of these measurements with chemical measurements taken of both cortical as well as trabecular bone. The limitations inherent in using the current technology to measure the bones of adolescents have been identified. Finally, project investigators have reviewed issues related to lead toxicity in elderly adults.