Polymorphisms inXPCandXPDgenes modulate DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India

摘要

The genetic susceptibility of individuals to the genotoxic effect of pesticides may be modulated by variations in genes involved in nucleotide excision repair (NER) pathway and therefore plays an important role in the evaluation of occupational risk. We aimed to evaluate the role of xeroderma pigmentosum complementation group C (XPC) Lys939Gln (A2920C, rs2228001),XPCAla499Val (C2151T, rs2228000), xeroderma pigmentosum complementation group D (XPD) Asp312Asn (G23591A, rs1799793) andXPDLys751Gln (A35931C, rs13181) in the modulation of DNA damage. A total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls) from Punjab, North-West India were recruited to study DNA damage by alkaline comet assay. Genotyping was carried out by PCR-RFLP using site-specific restriction enzymes. We found significant elevation in DNA damage parameters in pesticide-exposed agricultural workers as compared to the controls (p < 0.01). Association of comet tail length withXPC939Gln/Gln (CC),XPD312Asp/Asn (GA) andXPD312Asn/Asn (AA) genotypes was observed. Frequency of cells showing DNA migration was significantly higher in exposed workers with variantXPC939Gln/Gln (CC),XPD312Asp/Asn (GA) andXPD312Asn/Asn (AA) genotypes. Mean tail length was significantly increased in agricultural workers carryingXPD312Asn/Asn (AA) genotype. Elevation in total comet DNA migration was also observed in exposed workers carrying variantXPC939Lys/Gln (AC),XPC939Gln/Gln (CC),XPC499Val/Val (TT) andXPD312Asn/Asn (AA) genotypes. Our results strongly indicate significant positive association of variantXPCandXPDgenotypes with higher pesticide-induced DNA damage in North-West Indian agricultural workers.