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Single nucleotide polymorphisms (SNPs) in metabolic enzymes and their influence on neurobehavioral response to chronic solvent exposure.

Qian-H; Hong-J; Wang-S; Fiedler-N; Weisel-C
Toxicologist 2009 Mar; 108(1):249
Chronic exposure to solvent derived Volatile Organic Compounds during bridge painting has been associated with adverse neurobehavioral outcomes. This relationship could be modified by an individual's unique genetic make-up. Polymorphisms in enzymes involved in the metabolism of organic solvents could potentially increase neuropsychological impairment susceptibility from solvent exposures. In this study, we've identified five known human neurotoxicants: ethyl acetate, methyl ethyl ketone, toluene, xylene, and n-hexane, from air samples collected during bridge painting from 2005 to 2007 in New York, New Jersey, and Pennsylvania. Based on enzymes kinetics, ten metabolic enzymes of these neurotoxicants were selected, including CYP2E1, CYP1A1, ALDH2, NAT1, NAT2, GSTM1, GSTT1, GSTP1, SOD1, and EPHX1. Twenty six SNPs in the ten metabolic enzymes which have potential to significantly modify the enzyme activities were genotyped using SNPstream instrument. The frequencies of the variant alleles in the Caucasian painters (n=84) are 14.88% for CYP1A1*2A, 25.00% for NAT2*6A, 32.14% for GSTM1 null genotype, 25.00% for GSTT1 null genotype, 43.10% for GSTP1a, 24.07% for EPHX1*3 and 15.48% for EPHX1*4. Other genetic variants genotyped had frequencies below 10% in the study population, thus the study has insufficient power to determine their role in modifying neurobehavioral response. A dose-response relationship is determined between an estimate of a painter's lifetime solvent exposure reconstructed from a questionnaire completed by each painter and his neurobehavioral effects on attention, working and visual memory from the Cambridge Neuropsychological Test Automated Batteries. The modification effects of these genetic polymorphisms on the dose-response relationship then are examined using multivariate regression analysis, adjusted with confounding factors: age, education, body mass index, and lifetime alcohol consumption.
Absorption-rates; Biological-effects; Biological-factors; Behavior-patterns; Dose-response; Exposure-assessment; Exposure-levels; Exposure-methods; Genetic-factors; Metabolic-activation; Metabolic-study; Metabolism; Neurological-reactions; Neurotoxic-effects; Occupational-exposure; Organic-compounds; Organic-vapors; Organic-solvents; Painters; Painting; Psychological-effects; Psychological-processes; Psychological-reactions; Psychological-responses; Questionnaires; Statistical-analysis
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The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
Performing Organization
University of Medicine/Dentistry - NJ, Robert Wood Johnson Medical School