Impact of OGG1 and PARP1 Variants on Lead and Cadmium Induced DNA Damage in Metal Handicraft Workers of Jodhpur.

Workers in the metal handicraft industry are frequently exposed to heavy metals such as lead and cadmium, which are known to induce oxidative DNA damage. Individual susceptibility to this damage may be influenced by genetic variations in DNA repair enzymes, particularly 8-oxoguanine DNA glycosylase 1 (OGG1) and poly(ADP-ribose) polymerase 1 (PARP1). This study examined the combined effects of metal exposure and single nucleotide polymorphisms (SNPs) in DNA repair genes, namely OGG1 rs1052133 (Ser326Cys) and PARP1 rs1136410 (Val762Ala). A cross-sectional study was conducted involving 90 workers exposed to metals and 90 age and gender matched controls. Blood levels of lead and cadmium were measured by atomic absorption spectrophotometry. Oxidative DNA damage was assessed by serum levels of 8-hydroxy-2′-deoxyguanosine, while expression of OGG1 and PARP1 was evaluated by real-time PCR. Genotyping was performed using the PCR-RFLP method, and regression analyses were applied to identify independent predictors of DNA damage. Lead and cadmium levels were significantly elevated in exposed workers (p < 0.001), accompanied by increased 8-OHdG (p < 0.01) and downregulation of OGG1 and PARP1 (p < 0.001). OGG1 rs1052133 followed a dominant pattern with reduced expression in G-allele carriers (p = 0.008), while the PARP1 rs1136410 G/G genotype, consistent with a recessive model, emerged as a predictor of oxidative damage. Regression analysis confirmed Pb exposure and PARP1 rs1136410 G/G as significant predictors, whereas Cd and OGG1 rs1052133 showed no effect. These findings indicate that lead exposure is strongly associated with oxidative DNA damage, with genetic susceptibility potentially influencing individual risk.