Impact of single nucleotide polymorphisms in the OGG1 and XRCC1 genes on modulation of DNA damage in pesticide-exposed agricultural workers in Punjab, North-West India

摘要

Pesticide-induced DNA damage is primarily repaired by base excision repair (BER) pathway. However, polymorphism in DNA repair genes may modulate individual's DNA repair capacity (DRC) leading to increased genotoxicity and adverse health effects. Our first study in North-West Indian population aimed to evaluate the impact ofOGG1rs1052133 (Ser326Cys; C1245G),XRCC1rs1799782 (Arg194Trp; C26304T) andXRCC1rs25487 (Arg399Gln; G28152A) polymorphisms on the modulation of pesticide-induced DNA damage in a total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls). DNA damage was estimated by alkaline comet assay using silver-staining method. Genotyping was carried out by PCR-RFLP using site-specific restriction enzymes. Mann-Whitney U-test revealed elevation in DNA damage parameters (p 0.01) in pesticide-exposed agricultural workers than controls. Chi-square test showed significant (p 0.05) differences in theXRCC1Arg194Trp (C26304T) and Arg399Gln (G28152A) genotypes among two groups. Multivariate logistic-regression analysis revealed that heterozygous genotypes ofOGG1rs1052133 (326Ser/Cys; 1245CA),XRCC1rs1799782 (194Arg/Trp; 26304CT) andXRCC1rs25487 (399Arg/Gln; 2815GA) were positively associated (p 0.05) with elevated DNA damage parameters in pesticide-exposed agricultural workers. Our results strongly indicate significant positive association of variantOGG1andXRCC1genotypes with reduced DRC and higher pesticide-induced DNA damage in North-West Indian agricultural workers.