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. 2020 May 23;6(5):e03993.
doi: 10.1016/j.heliyon.2020.e03993. eCollection 2020 May.

The association between PON1 and GSTM1 genetic variation with methylation of p16 gene promoter among Javanese farmers exposed to pesticides at Magelang Regency, Central Java, Indonesia

Maya G Ratna  1 , Dwi A A Nugrahaningsih  2   3 , Eti N Sholikhah  2 , Ery K Dwianingsih  4   3 , Rusdy G Malueka  5   3
Affiliations

The association between PON1 and GSTM1 genetic variation with methylation of p16 gene promoter among Javanese farmers exposed to pesticides at Magelang Regency, Central Java, Indonesia

Maya G Ratna et al. Heliyon. .

Abstract

Occupational exposure to pesticides leads to the development of cancer. Aberrant DNA methylation plays a crucial role in cancer. The manifestation of the carcinogenic effect of pesticides could be determined by the variation of genes encoding enzyme, including PON1 Q192R and GSTM1. The goal of this study was to find out polymorphism of PON1 Q192R and methylation of p16 gene promoter, and their correlation on Javanese farmers in the agricultural area of Ngablak Subdistrict, Magelang Regency, Central Java. Seventy-eight pesticide-exposed farmers enrolled in the study. Polymorphism of PON Q192R was determined using PCR-RFLP and variation of GSTM1 was examined using conventional PCR. The methylation of the p16 gene promoter was determined using methylation-specific PCR. The result revealed 94.9% polymorphism of PON1 Q192R, which was higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes. We also found 82.1% GSTM1 null genotype among the farmers enrolled in the study. As many as 26.9% methylations of p16 gene promoter were found among farmers. Genetic variation of PON1 Q192R and GSTM1 were not found to be correlated to the methylation status of p16 gene promoter in the Javanese population.

Keywords: Cancer; Environment; Environmental pollution; Environmental toxicology; GSTM1 pesticides; Genetics; Methylation of p16 gene promoter; Pharmacology; Polymorphism of PON1 Q192R; Public health; Toxicology.

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Figures

Figure 1
Figure 1
The PON1 Q192R. 175 and 63 bp showed mutant allele (RR), undigested 238 bp showed wild type allele (QQ), and all 238, 175, and 63 bp showed heterozygous allele (QR). Please see supplementary file for the corresponding original image.
Figure 2
Figure 2
The GSTM1, 219 bp showed positive genotype. Please see supplementary file for the corresponding original image.
Figure 3
Figure 3
Methylation status of p16 gen promoter. U lane shows un-methylation (151 bp). M lane shows methylation (150 bp). W lane is bisulfate modification control (141 bp). Positive control is a M.Sssi treated DNA. Negative control is an unmodified DNA control. Water (H2O) is a control for PCR. Please see supplementary file for the corresponding original image.
See this image and copyright information in PMC

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