GST CYP and PON1 polymorphisms in farmers attributing ill health to organophosphate-containing sheep dip.
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.
Povey
A C
AC
Centre for Occupational and Environmental Health, University of Manchester, UK. apovey@manchester.ac.uk
Jury
F
F
Dippnall
W M
WM
Smith
A E
AE
Thomson
S
S
Mackness
B
B
Mackness
M
M
Durrington
P
P
Cherry
N M
NM
D000383:Agriculture; D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007306:Insecticides / Q000009:adverse effects; D016273:Occupational Exposure / Q000009:adverse effects*; D010755:Organophosphates / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D034561:Sheep, Domestic
D043303:Aryldialkylphosphatase; D019389:Cytochrome P-450 CYP2D6; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007306:Insecticides; D010755:Organophosphates; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human