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Walter F. Stewart,¹ Brian S. Schwartz,^1,2,3 David Simon,¹ Karl Kelsey,⁴ and Andrew C. Todd ⁵

¹Department of Epidemiology, and ²Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; ³Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; ⁴Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts, USA; ⁵Department of Community and Preventive Medicine, Mount Sinai Medical Center, New York, New York, USA

Abstract

Our objective in this study was to determine if the known relation between tibia bone lead levels and neurobehavioral test scores are influenced by the apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests in 529 former organolead workers who had an average of 16 years since last occupational exposure to lead. We used linear regression to model the relations between each of 20 neurobehavioral test scores and tibia lead, a binary variable for ApoE genotype (i.e., at least one 4 allele vs. none) , and an interaction term between tibia lead and the binary term for ApoE genotype. At the time of testing, former lead workers were an average of 57.6 years of age ; 82% were younger than 65 years. In regression analysis, we observed one statistically significant and one borderline significant coefficient for ApoE genotype alone. Coefficients for the ApoE and tibia lead interaction term were negative in 19 of the 20 regression models. This indicates that the slope for the relation between tibia lead and each neurobehavioral test was more negative for individuals with at least one 4 allele than for those who did not have an 4 allele. Four of 19 negative coefficients for the interaction term were statistically significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant hand, complex reaction time) ; another three of the remaining 16 coefficients (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p < 0.10) . This study suggests that individuals may vary in susceptibility to the long-term effects of lead on the central nervous system (CNS) . In particular, the persistent CNS effect of lead may be more toxic in individuals who have at least one ApoE-4 allele. Key words: apolipoprotein E, bone lead, cognitive function, neurobehavioral tests, X-ray fluorescence.Environ Health Perspect 110:501-505 (2002) . [Online 2 April 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p501-505stewart/ abstract.html

Address correspondence to W. Stewart, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Room 6027, 615 North Wolfe Street, Baltimore, MD 21205 USA. Telephone: (410) 955-3906. Fax: (410) 955-0863. E-mail: wstewart@jhsph.edu

We thank M. Liu for work involved in apolipoprotein genotyping.

This research was supported by grant RO1 AG10785 from the National Institute on Aging (NIA) and grants P42 ES-05947 and ES00002 from the National Institute of Environmental Health Sciences (NIEHS) , with funding provided by the U.S. Environmental Protection Agency (U.S. EPA) . The content of this article is solely the responsibility of the authors and does not necessarily represent official views of the NIA, NIEHS, or U.S. EPA.

Received 9 October 2001 ; accepted 4 December 2001.