Modulation of DNA damage by XPF, XPG and ERCC1 gene polymorphisms in pesticide-exposed agricultural workers of Punjab, North-West India

Abstract

Inter-individual variations in DNA repair capacity (DRC) for repairing pesticide-induced DNA oxidation damage may influence adverse health outcomes. We aimed to evaluate whether polymorphisms in genes involved in nucleotide excision repair (NER) pathway could modulate DNA damage in pesticide-exposed agricultural workers. Xeroderma pigmentosum group F (XPF) (Arg415Gln, G1244A, rs1800067), xeroderma pigmentosum group G (XPG) (Asp1104His, G3507C, rs17655), excision repair cross complementation group 1 (ERCC1) (3′UTR, C8092A, rs3212986) and ERCC1 (Asn118Asn, C19007T, rs11615) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 225 pesticide-exposed agricultural workers and 225 controls from Punjab, North-West India. The assessment of DNA damage was carried out by alkaline comet assay. Kruskal-Wallis test was used to evaluate the association of gene polymorphisms in NER pathway with DNA damage. Pesticide-exposed agricultural workers carrying variant XPF Gln/Gln (AA) genotype showed higher comet tail length (p < 0.01) than wild type Arg/Arg (GG) genotype. The comet tail length (p < 0.01) was found to be significantly increased in exposed agricultural workers carrying XPG His/His (CC) genotype than wild-type Asp/Asp (GG) genotype. In relation to the individuals carrying wild type ERCC1 3′UTR CC genotype, exposed individuals with variant ERCC1 3′UTR CA genotype showed elevation in the comet tail length (p = 0.029). However, we found no association of ERCC1 Asn118Asn (C19007T) genotype with DNA damage. These results indicate that XPF, XPG and ERCC1 genes of NER pathway may modulate the efficacy of the DNA repair system against pesticide exposure in our population.