Paraoxonase 1 gene polymorphism and enzymatic activity as a prognostic marker in cases of poisoning by cholinesterase inhibitor pesticides among Egyptians

Abstract

Paraoxonase1 (PON1) is a high-density lipoprotein associated A-esterase capable of hydrolysing activated metabolites (oxons) of several pesticides as organophosphorous, including chlorpyrifos, diazinon as well as carbamates. Human PON1 displays polymorphisms in the coding region (Q192R and L55M) and in the promoter and the 3’-UTR regions. Animal studies showed that high levels of PON1 protect individuals against acute organophosphatespoisoning. The PON1 genotype and enzymatic activity together contribute to determining an individual's PON1 “status”. In this study, the role of PON1 gene polymorphismsand its enzymatic activity was assessed as a prognostic marker in cases of acute poisoning by cholinestersase inhibitor (ChEI) pesticides among a sample of Egyptian population. Two equal groups of 100 unrelated individuals participated in the study: an exposed group and non-exposed group as control. Serum paraoxonase1 enzyme activitymeasured as arylesterase activity spectrophotometrically using the substrate phenyl acetate. PON1 Q192R gene was genotyped using PCR-RFLP technique. The PON1 Q192R genotype frequency distribution in control subjects was (QQ=64%, QR=28%, RR=8%) and in patients was (QQ=54%, QR=42%, RR=4%) and this was statistically significant (p=0.029). The arylesterase activity was significantly higher in control than exposed group (p=0.037). Regarding the effect of Q192R genotype and arylesterase activity on the outcome, there was no significant difference between the good and poor prognosis groups. Evaluation of PON1 status may be important for determining individual susceptibility to poisoning by ChEI pesticides. However, the estimated level of arylesterase after exposure to poisoning can’t be used in prediction of prognosis. Moreover, the coding genes show discrepant results even within the same ethnic group.