Pyrethroid exposure: as determinant of CYP1A1 and GSTP1 genetic variations in occupationally exposed Sindh farmers

Abstract

Pyrethroid (PYR) is a class of pesticide which was frequently applied in agricultural fields of Sanghar in Pakistan. Consistent and over use of PYR may lead to health effects on workers who are occupationally exposed to pesticides every day. For assessment of PYR toxicity, Cytochrome-P450 (CYP1A1) and Glutathione–S-transferase P1 (GSTP1) code for xenobiotic metabolizing enzymes (XME) were investigated in Sanghar exposed studied population. To execute the case-control study, a total of 200 blood samples from PYR-exposed and control subjects were collected. Prior informed consent was taken from all the subjects. For determination of genetic variations, CYP1A1 (rs1048943) and GSTP1 (rs1695) regions were amplified using polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). Resolved bands were visualized on 2 % agarose gel. Results indicated that in CYP1A1 polymorphism (rs1048943) there was no significant association between CYP1A1 genotypes AA, AG, GG and PYR toxicity (ϰ2= 2.03, p > 0.05) in exposed subjects. However, the impact of mutant allele G was further evaluated by genetic models, which demonstrated that G allele may show a risk for CYP1A1gene susceptibility to PYR exposure (OR: 8.608; CI: 1.056–70.172) p < 0.05 in dominant and in co-dominant model (OR:16.25; CI:1.94-135.84) p < 0.05 as well. In contrast, in GSTP1 (rs1695) polymorphism, a significant association was observed in genotypes AA, AG, GG (ϰ2= 8.03, p < 0.05) compared with control subjects. G allele may also exhibit a significant association with GSTP1 gene susceptibility and PYR-toxicity in co-dominant model (OR: 7.166; CI: 2.828–8.15) p < 0.001. This study may help to provide acquaintance about the pesticide hazardous effects.