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

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.

[1]  C. Sukasem,et al.  Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population , 2021, Scientific Reports.

[2]  I. Subekti,et al.  Cumulative exposure characteristics of vegetable farmers exposed to Chlorpyrifos in Central Java – Indonesia; a cross-sectional study , 2021, BMC Public Health.

[3]  Jen Fuk Liem.  Biomonitoring Pajanan Pestisida Organofosfat pada Pekerja Pertanian , 2021, Jurnal Kedokteran Meditek.

[4]  F. Guengerich,et al.  Human Family 1–4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update , 2021, Archives of Toxicology.

[5]  I. Setyopranoto,et al.  The Association between Pesticide Exposure and Neurological Signs and Symptoms in Farmers in Magelang District, Central Java, Indonesia , 2020 .

[6]  H. H. Nguyen,et al.  CYP2C19 genetic polymorphism in the Vietnamese population , 2019, Annals of human biology.

[7]  C. Fenga,et al.  Genetic polymorphisms as determinants of pesticide toxicity: Recent advances , 2019, Toxicology reports.

[8]  Sherry‐Ann Brown,et al.  Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine , 2018, Journal of personalized medicine.

[9]  J. Casida,et al.  The ABCs of pesticide toxicology: amounts, biology, and chemistry. , 2017, Toxicology research.

[10]  Yitian Zhou,et al.  Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects , 2017, Clinical pharmacology and therapeutics.

[11]  Ajai Kumar Jain,et al.  CYP/PON genetic variations as determinant of organophosphate pesticides toxicity , 2017, Journal of Genetics.

[12]  H. Rodriguez,et al.  Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[13]  M. Bonner,et al.  Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators , 2014, BMJ Open.

[14]  U. Zanger,et al.  Effect of CYP2B6*6 and CYP2C19*2 genotype on chlorpyrifos metabolism. , 2012, Toxicology.

[15]  J. Olson,et al.  Allele and Genotype Frequencies of CYP2B6 and CYP2C19 Polymorphisms in Egyptian Agricultural Workers , 2012, Journal of toxicology and environmental health. Part A.

[16]  Corie A Ellison,et al.  Cytochrome P450-specific human PBPK/PD models for the organophosphorus pesticides: chlorpyrifos and parathion. , 2011, Toxicology.

[17]  M. Ingelman-Sundberg,et al.  Genetic polymorphism and toxicology--with emphasis on cytochrome p450. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  D. Nelson,et al.  Cytochrome P450 (CYP) Gene Superfamily , 2011 .

[19]  Songnian Hu,et al.  Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese , 2009, The Pharmacogenomics Journal.

[20]  M. Hiratsuka,et al.  Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. , 2002, British journal of clinical pharmacology.

[21]  N. Rothman,et al.  A quantitative approach for estimating exposure to pesticides in the Agricultural Health Study. , 2002, The Annals of occupational hygiene.

[22]  J. Goldstein,et al.  Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. , 1997, Pharmacogenetics.

[23]  G R Wilkinson,et al.  The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. , 1994, The Journal of biological chemistry.