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Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE.

Howard TD, Hsu FC, Grzywacz JG, Chen H, Quandt SA, Vallejos QM, Whalley LE, Cui W, Padilla S, Arcury TA - Environ. Health Perspect. (2010)

Bottom Line: Organophosphate pesticides act as cholinesterase inhibitors.A false discovery rate (FDR) p-value was used to account for multiple testing.Thirty-five SNPs were associated (unadjusted p < 0.05) based on at least one of the genetic models tested (general, additive, dominant, and recessive).

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. tdhoward@wfubmc.edu

ABSTRACT

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.

Objectives: 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.

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Related in: MedlinePlus

Genetic ancestry of PACE3 participants based on principal component analysis (PCA) with International HapMap samples. Three principal components (PCA1–PCA3) are shown that discriminate the HapMap samples from Northern European (CEU), Yoruban in Ibadan, Nigeria (YRI), Chinese (CHB), and Japanese (JPT) genetic ancestry. Each panel is a plot of two principal component values. PACE3 individuals cluster between the CEU and Asian populations.
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f1-ehp-118-1395: Genetic ancestry of PACE3 participants based on principal component analysis (PCA) with International HapMap samples. Three principal components (PCA1–PCA3) are shown that discriminate the HapMap samples from Northern European (CEU), Yoruban in Ibadan, Nigeria (YRI), Chinese (CHB), and Japanese (JPT) genetic ancestry. Each panel is a plot of two principal component values. PACE3 individuals cluster between the CEU and Asian populations.

Mentions: Most of the individuals in PACE3 reported being of Mexican descent. Principal component analysis with the 34 AIMs was consistent with this designation, because most of the of individuals clustered between the HapMap samples for individuals of Northern European (CEU) and Asian (CHB and JPT) genetic ancestry (Figure 1). Principal component 1 clearly distinguished the Yoruban population, whereas principal component 2 provided the best separation between the Northern European and Asian populations.


Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE.

Howard TD, Hsu FC, Grzywacz JG, Chen H, Quandt SA, Vallejos QM, Whalley LE, Cui W, Padilla S, Arcury TA - Environ. Health Perspect. (2010)

Genetic ancestry of PACE3 participants based on principal component analysis (PCA) with International HapMap samples. Three principal components (PCA1–PCA3) are shown that discriminate the HapMap samples from Northern European (CEU), Yoruban in Ibadan, Nigeria (YRI), Chinese (CHB), and Japanese (JPT) genetic ancestry. Each panel is a plot of two principal component values. PACE3 individuals cluster between the CEU and Asian populations.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957918&req=5

f1-ehp-118-1395: Genetic ancestry of PACE3 participants based on principal component analysis (PCA) with International HapMap samples. Three principal components (PCA1–PCA3) are shown that discriminate the HapMap samples from Northern European (CEU), Yoruban in Ibadan, Nigeria (YRI), Chinese (CHB), and Japanese (JPT) genetic ancestry. Each panel is a plot of two principal component values. PACE3 individuals cluster between the CEU and Asian populations.
Mentions: Most of the individuals in PACE3 reported being of Mexican descent. Principal component analysis with the 34 AIMs was consistent with this designation, because most of the of individuals clustered between the HapMap samples for individuals of Northern European (CEU) and Asian (CHB and JPT) genetic ancestry (Figure 1). Principal component 1 clearly distinguished the Yoruban population, whereas principal component 2 provided the best separation between the Northern European and Asian populations.

Bottom Line: Organophosphate pesticides act as cholinesterase inhibitors.A false discovery rate (FDR) p-value was used to account for multiple testing.Thirty-five SNPs were associated (unadjusted p < 0.05) based on at least one of the genetic models tested (general, additive, dominant, and recessive).

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. tdhoward@wfubmc.edu

ABSTRACT

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.

Objectives: 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.

Show MeSH
Related in: MedlinePlus