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.

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.

The analysis of DMD gene deletions by multiplex PCR in Indonesian DMD/BMD patients: the era of personalized medicine.

OBJECTIVE: Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common genetic neuromuscular disease in children, resulting from a defect in the DMD gene located on Xp21.2. The new emerging treatment using exon skipping strategy is tailored to specific mutations, thus molecular diagnostics are particularly important. This study aimed to detect the DMD gene deletion in Indonesian DMD/BMD patients and analyze the potential amenability by exon skipping therapy. RESULTS: Thirty-four male patients were enrolled in this study, 23 of them (67.6%) underwent muscle biopsy and showed the absence or partially expressed dystrophin protein in immunohistochemistry staining. All patients had very high serum CK levels (10.529 ± 9.97 IU/L). Multiplex PCR revealed the DMD gene deletions in 15 (44.1%) cases. Seventy-eight percent of deletions were clustered in the hot-spot region of exon 43 to 52. Furthermore, seven (20.5%) patients were potentially amenable to exon skipping treatment. Therefore, multiplex PCR is one feasible method to detect DMD gene deletion in Indonesian DMD/BMD patients that can further determine the potential amenability of exon skipping therapy. In addition, this study is the first report of DMD gene deletion analysis in Indonesia.