Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE.
BACKGROUND
Organophosphate pesticides act as cholinesterase inhibitors. For those with agricultural exposure to these chemicals, risk of potential exposure-related health effects may be modified by genetic variability in cholinesterase metabolism. 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.


OBJECTIVE
We studied participants in the Community Participatory Approach to Measuring Farmworker Pesticide Exposure (PACE3) study to determine whether cholinesterase levels 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 up to four time points during the 2007 growing season. We performed association tests of cholinesterase levels and 256 SNPs in 30 candidate genes potentially involved in pesticide metabolism. A false discovery rate (FDR) p-value was used to account for multiple testing.


RESULTS
Thirty-five SNPs were associated (unadjusted p < 0.05) based on at least one of the genetic models tested (general, additive, dominant, and recessive). The strongest evidence of association with cholinesterase levels was observed with two SNPs, rs2668207 and rs2048493, in the butyrylcholinesterase (BCHE) gene (FDR adjusted p = 0.15 for both; unadjusted p = 0.00098 and 0.00068, respectively). In participants with at least one minor allele, cholinesterase levels were lower by 4.3-9.5% at all time points, consistent with an effect that is independent of pesticide exposure.


CONCLUSIONS
Common genetic variation in the BCHE gene may contribute to subtle changes in cholinesterase levels.
Howard
Timothy D
TD
Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. tdhoward@wfubmc.edu
Hsu
Fang-Chi
FC
Grzywacz
Joseph G
JG
Chen
Haiying
H
Quandt
Sara A
SA
Vallejos
Quirina M
QM
Whalley
Lara E
LE
Cui
Wei
W
Padilla
Stephanie
S
Arcury
Thomas A
TA
D000293:Adolescent; D000328:Adult; D000383:Agriculture; D002091:Butyrylcholinesterase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide
D009943:Organophosphorus Compounds; D010575:Pesticides; D002091:Butyrylcholinesterase