Evaluation of the influence of chronic low-dose radiation on DNA repair gene polymorphisms [ XRCC1, XRCC3, PRKDC (XRCC7), LIG1, NEIL1] in individuals from normal and high level natural radiation areas of Kerala Coast

Abstract

Background: Single Nucleotide Polymorphisms (SNPs) at DNA repair genes are considered as potential biomarkers of radio-sensitivity. The coastal belt of Kerala in south west India has a patchy distribution of monazite in its beach sand that contains Th-232 and its decay products. Thus, radiation levels in this area vary from <1.0mGy to 45.0mGy/year. The areas with external gamma radiation dose >1.5mGy/year are considered as High-Level Natural Radiation Areas (HLNRA) and ≤ 1.5mGy/year are Normal Level Natural Radiation Area (NLNRA).Objective: In the present study, an attempt was made to evaluate the influence of chronic low dose radiation exposure on DNA repair gene polymorphisms in NLNRA and HLNRA population of Kerala coast.Materials and methods: Genomic DNA was isolated from venous blood samples of 246 random, healthy individuals (NLNRA, N = 104; HLNRA, N = 142) and genotyping of five SNPs such as X-ray repair cross complementing 1(XRCC1 Arg399Gln), X-ray repair cross complementing 3 (XRCC3 Thr241Met], Protein kinase, DNA-activated, catalytic subunit (PRKDC) (X-ray repair cross-complementing group 7, XRCC7 G/T), nei like DNA glycosylase 1 (NEIL1 G/T) and DNA ligase 1 (LIG1 A/C) was carried out using PCR based restriction fragment length polymorphism (PCR-RFLP) followed by silver staining.Results: Our results showed no significant difference in genotype frequencies in HLNRA vs NLNRA at three of the five SNPs studied i.e. XRCC1 Arg399Gln (χ²₍₂₎ = 5.85, p = .054), XRCC3 Thr241Met (χ²₍₁₎ = 0.71, p = .339), PRKDC (XRCC7 G/T) (χ²₍₂₎ = 3.72, p = .156), whereas significant difference was observed at NEIL1 G/T (χ²₍₂₎ =8.71, p = .013) and LIG1 A/C (χ²₍₂₎ = 7.66, p = .022). The odds of heterozygote to homozygote genotypes in HLNRA relative to NLNRA at XRCC1 Arg399Gln (OR = 1.96, 95% CI: 1.13-3.40), XRCC3 Thr241Met (OR = 0.73, 95% CI: 0.41-1.31), PRKDC (XRCC7 G/T), (OR = 0.81; 95% CI: 0.48-1.38), NEIL1 G/T (OR = 0.54; 95% CI: 0.31-0.96) and LIG1 A/C (OR = 1.62; 95% CI: 0.97-2.69) was also not significantly different in HLNRA vs NLNRA, except at XRCC1 and NEIL1.Conclusion: The genotype frequencies at three of these SNPs i.e. XRCC1 Arg399Gln, XRCC3 Thr241Met and PRKDC (XRCC7 G/T) were similar, whereas NEIL1 G/T and LIG1 A/C showed significant difference between HLNRA and NLNRA population. However, further research using more number of SNPs in a larger cohort is required in this study area.

Keywords: DNA repair gene polymorphism; PCR based restriction fragment length polymorphism; genomic DNA; high and normal level natural radiation area.