Polimorfismo de CYP2C9: estudo da relação do uso de agrotóxicos com o desenvolvimento de doenças em agricultores do Espírito Santo

Abstract

B razil is the leader of the world ranking in consumption of pesticides. The indiscriminate use of pesticides associated with the lack of technical information on the use of the same and of personal protective equipment (PPE), can put the health of both the farmer and people who are not in direct contact with the crop, such as family members, at risk and even final consumer of the agricultural product. The Cytochrome P450 (CYP) superfamily has been the focus of most recent pharmacogenetic research and, in this context, the CYP2C9 gene stands out for encoding the CYP2C9 enzyme, extremely important for the metabolism of several endogenous substances and specific xenobiotics. Among the main xenobiotics under investigation today are the pesticides (and potential causers of diseases in humans). Its indiscriminate use associated with the lack of technical information about safety, handling, and the use of personal protective equipment (PPE) can put place the farmer's health at risk. Based on this hypothesis, the general objective of this work was to verify the risk of the use of pesticides for the development of diseases and its correlation with two important CYP2C9 polymorphisms in farmers living in the southern region of the State of Espirito Santo, Brazil. For this purpose, the allele frequency of CYP2C9 *1 (wild allele), CYP2C9 *2 (rs1799853) and CYP2C9 *3 (rs1057910) in 304 samples of peripheral blood from individuals exposed or not exposed to pesticides were determined by real-time PCR technique. The allele frequency data obtained in this research were similar to those of three other brazilian studies, with the *1 and *3 alleles being the most and least occurring, respectively. The different CYP2C9 genotypes were divided into classes according to the metabolism capacity of that enzyme: normal or “A” (*1/*1), intermediate or “B” (*1/*2, *1/*3) and slow or “C” (*2/*2,*2/*3 and *3/*3). Significant associations were found between CYP2C9 genotypes and the appearance of diseases/symptoms only in farmers who used pesticides. Surprisingly, the results obtained demonstrated that normal metabolizers are more susceptible to the development of some diseases/symptom in relation to metabolic “B” and “C” individuals. Still in the “A” metabolizers, was noted a correlation with changes in blood pressure, cardiovascular diseases and kidney diseases, while for the intermediate metabolizers an association was observed with the appearance of attention deficit and abortions. No statistically significant results were found for slow metabolizers. Our results indicate that farmers in the southern State of Espirito Santo who used pesticides developed/presented changes in blood pressure, cardiovascular and kidney diseases, in addition to abortion and attention deficit, in a dependent and correlated manner to the CYP2C9 genotype they have