Relationship between human paraoxonase-1 activity and PON1 polymorphisms in Mexican workers exposed to organophosphate pesticides

I López-Flores, M Lacasaña, J Blanco-Muñoz, C Aguilar-Garduño, P Sanchez-Villegas, O A Pérez-Méndez, R Gamboa-Avila
Toxicology Letters 2009 July 24, 188 (2): 84-90
Paraoxonase-1 (PON1) is a serum enzyme which catalyzes the hydrolysis of organophosphate pesticides. In this study we conducted a cross-sectional study and reported on the distribution of three common genetic polymorphisms of the PON1 gene in a population of floriculture workers from Mexico as well as the association between those polymorphisms and other predictors with serum PON1 activity on paraoxon, diazoxon and phenylacetate. The genotype frequencies at position PON1(55) were 89% (LL), 10% (LM) and 0.6% (MM), at position PON1(192) they were 16% (QQ), 47% (QR) and 37% (RR), and 26% (TT), 42% (TC) and 32% (CC) at position PON1(-108). Thus, the frequencies of alleles L, Q and T were 0.94, 0.40 and 0.47, respectively. The PON1(55) polymorphism had no significant effect on serum PON1 activity on any substrate. We found a significant association between the PON1(192) polymorphism and PON1 activity towards paraoxon and diazoxon, which increased in genotypes as follows: 192RR>192QR>192QQ for paraoxonase activity and, inversely, 192QQ>192QR>192RR for diazoxonase activity. The PON1(-108) polymorphism also had a significant effect on PON1 activity level towards paraoxon in the following order among the genotype groups: -108CC>-108TC>-108TT. Serum PON1 activity towards diazoxon was not associated with the PON1(-108) polymorphism but it was influenced by the intensity exposure to pesticides at the floriculture industry and the years of the occupational exposure to pesticides. No polymorphism significantly influenced serum PON1 activity on phenylacetate.


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