Prevalence of CYP2C19 681G>A and 636G>A Gene Polymorphisms in Javanese Farmers Exposed to Chlorpyrifos

Abstract

Objective. The objective of our study was to determine the genotype frequencies of CYP2C19*2 and *3 gene polymorphisms among Javanese farmers exposed to chlorpyrifos (CPF) in Central Java, Indonesia.
 Methods. This cross-sectional study was conducted from July to October 2020 in Central Java, Indonesia, involving 151 vegetable farmers aged 18-65 years who used CPF for at least one year. CYP2C19*2 and *3 gene polymorphisms were analyzed using PCR-RFLP. Direct calculations were applied to calculate allele and genotype frequencies. The difference in genotype frequencies among the sex and cumulative exposure level (CEL) group was performed using the Chi-square test. In contrast, the proportion difference of allele frequencies was analyzed using Z-test.
 Results. The frequency of CYP2C19 genotypes *1/*1, *1/*3, *1/*2, and *2/*2 were 64 %, 7 %, 23 % and 6 %. We observed no significant difference in the genotype distribution according to sex group and CEL group.
 Conclusion. In summary, the prevalence of toxicologically relevant CYP2C19 polymorphisms was determined in the Javanese agricultural population. The CYP2C19 genotype may be helpful as an essential biomarker of genetic susceptibility towards CPF exposure. Nevertheless, further studies to confirm the role of CYP2C19 in this context are still needed.

Human CYP2C19 Substrate and Inhibitor Characterization of Organophosphate Pesticides

“… The oxon is the active form of the pesticide, which inhibits AChE and confers the pesticide function; the thion form requires biotransformation (activation) into the oxon form to achieve toxicity . The interaction between specific OPPs and CYPs is a topic of interest, as several have been shown to favor either the activation or detoxification of different OPPs. − The interactions between CYPs and OPPs have been assessed in agricultural workers all over the world, in studies where workers have been genotyped for polymorphisms in the genes encoding CYP1A1 and 1A2, CYP2B6, CYP2D6, CYP2C19, CYP2E1, CYP3A4, and CYP3A5 in order to document prevalence of alleles in these populations and, in some cases, draw conclusions about specific mutations and health outcomes with OPP exposure. − In vitro studies using recombinant enzymes or liver microsomes to identify those responsible for the metabolism, either activation or detoxification, of OPPs consistently show CYP3A4, CYP2B6, and CYP2C19 to be among the most important. − ,, …”