Contrasting genetic influence of PON 1 coding gene polymorphisms L55M and Q192R on individuals’ response to environmental agents

Abstract

Background: Paraoxonase (PON1) is an A-esterase capable of hydrolyzing the active metabolites (oxons) of many organophosphorus (OP) insecticides. Human PON1 displays two polymorphisms in the coding region (Q192R and L55M) and several polymorphisms in the promoter and the 3′-UTR regions. Animal studies have shown that PON1 is an important determinant of OP toxicity though a direct satisfactory verification in humans is still lacking. Aim: To investigate the impact of polymorphisms in the PON1 coding region (Q192R and L55M) on individual sensitivity to OP poisoning. Subjects and methods: This study enrolled 42 subjects (21 females and 21 males, age range 1.5–53 years) diagnosed of acute OP poisoning. They were classified into 4 grades according to manifestations. All subjects were genotyped for the PON1 gene polymorphisms; Q192R and L55M using RFLP-PCR, then genotype frequencies were compared between different OP grades. Results: Genotype frequency distribution of PON1 L55M polymorphism among different OP poisoning grades revealed no significant difference (p > 0.05) between the four grades. In contrast, frequency distribution of PON1 Q192R polymorphism showed a highly significant (p < 0.001) difference between different grades of OP poisoning, with QQ genotype predominating in grade 4 with a frequency of 66.7%, followed by QR genotype (33.3%), while the RR and QR genotypes were similarly distributed in grade 1 with a frequency of 50% for each. Conclusion: The current results suggest a possible association between QQ genotype and poor OP poisoning prognosis.

Keywords

• Paraoxonase
• L55M
• Q192R
• Organophosphate
• Poisoning grade