GST, CYP and PON1 polymorphisms in farmers attributing ill health to organophosphate-containing sheep dip

A. C. Povey, F. Jury, W. M. Dippnall, A. E. Smith, S. Thomson, B. Mackness, M. Mackness, P. Durrington, N. M. Cherry

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Previously we reported that in sheep dippers exposed to organophosphates the frequency of paraoxonase (PON1) polymorphisms differed between those with or without self-reported ill health. We have now examined whether polymorphisms in other genes involved in xenobiotic metabolism alter disease risk in this population. There were elevated but non-significant risks associated with the CYP2D6 WT genotype (odds ratio (OR) 1.47, 95% CI 0.83-2.60), or a GSTP1*B or *C allele (OR 1.37, 95% CI 0.88-2.01) or being GSTM1*2/GSTT1*2 homozygous (OR 1.61, 95% CI 0.74-3.48). Similar results were generally obtained after the exclusion of subjects to obtain a more homogenous case-referent population: for double null GSTM1 and GSTT1 homozygotes the OR was 2.06 (95% CI 0.85-2.04). In those also likely to have been exposed to diazinon, risks associated with a GSTP1*B or *C allele (OR 1.82, 95% CI 0.92-3.63) or a GSTM1*2/GSTT1*2 homozygous (OR 2.60, 95% CI 0.72-10.42) were elevated but not to a significant extent. Risk associated with PON1 genotype and phenotype varied with CYP2D6 and GSTP1 genotype but not consistently with a priori hypotheses. Further work is necessary to delineate more clearly pathways of organophosphate activation and non-PON1 pathways of detoxification and to confirm whether CYP and GST polymorphisms alter disease risk in populations exposed to organophosphates.
    Original languageEnglish
    Pages (from-to)188-202
    Number of pages14
    JournalBiomarkers
    Volume12
    Issue number2
    DOIs
    Publication statusPublished - Mar 2007

    Keywords

    • CYP
    • GST
    • Organophosphates
    • Paraoxonase
    • PON1
    • Sheep dip

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