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Evaluation of Candidate Genes for cholinesterase Activity in Farmworkers Exposed to organophosphorous Pesticides-Association of SNPs in BCHE
PADILLA, S. J., T. D. Howard, H. Fang-Chi, J. G. Grzywacz, H. Chen, S. A. Quandt, Q. M. Vallejos, L. E. Whalley, W. Cui, AND T. A. Arcury. Evaluation of Candidate Genes for cholinesterase Activity in Farmworkers Exposed to organophosphorous Pesticides-Association of SNPs in BCHE. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 118(10):1395-1399, (2010).
To determine if cholinesterase levels in participants in the Community Participatory Approach to Measuring Farmworker Pesticide Exposure (PACE3) study are associated with single nucleotide polymorphisms (SNPs) involved in pesticide metabolism
Background: Organophosphate pesticides act as cholinesterase inhibitors, and as such may give rise to potential neurological effects. Cholinesterase activity is a useful, indirect measurement of pesticide exposure, especially in high-risk individuals such as farmworkers. To understand fully the links between pesticide exposure and potential human disease, analyses must be able to consider genetic variability in pesticide metabolism. Objectives: To determine if cholinesterase levels in participants in the Community Participatory Approach to Measuring Farmworker Pesticide Exposure (PACE3) study are associated with single nucleotide polymorphisms (SNPs) involved in pesticide metabolism. Methods: Cholinesterase levels were measured from blood samples taken from 287 PACE3 participants at four time points during the 2007 growing season. Association tests with cholinesterase levels and 256 SNPs in 30 candidate genes potentially involved in pesticide metabolism were performed. Results: Thirty-five SNPs were associated (p < 0.05) with at least one of the genetic models tested (general, additive, dominant, and recessive). The strongest evidence of association was observed with two SNPs -rs2668207 and rs2048493 -in the butyrylcholinesterase (BCHE) gene (p = 0.00098 and 0.00068, respectively). This association was observed with intrinsic cholinesterase levels, apparently independent of pesticide exposure. Participants with at least one minor allele had lower cholinesterase levels by 4.3 -9.5% at all time points. Conclusions: Common genetic variation in the BCHE gene contributes to subtle changes in cholinesterase levels, and these changes appear to be independent of pesticide exposure. It remains to be determined if these individuals are at an increased risk of chronic diseases associated with cholinesterase inhibition.