CORRELATION BETWEEN DNA REPAIR EFFICIENCY AND ACCUMULATION OF GENE MUTATIONS
Keywords:
DNA repair efficiency, genomic instability, mutation accumulation, DNA damage response, molecular biomarkers, precision medicine.Abstract
Background: Maintaining genome stability requires DNA repair mechanisms to repair the damages to DNA before they become permanent. If these repair mechanisms fail, mutations can slowly build up in the genome, and may make it more prone to different diseases. But data on the correlation between DNA repair capacity and mutation load in Pakistan population is scarce. The purpose of this study was to assess the correlation between DNA repair efficiency and gene mutation accumulation in people who visited a tertiary care hospital of Lahore, Pakistan.
Study Type: Experimental association study
Methods: An experimental association study was conducted with 120 participants from tertiary health care setting. Peripheral blood samples were drawn and genomic DNA was extracted for molecular studies. The ability to repair DNA was evaluated by quantifying the decrease in induced DNA damage after a fixed period of repair. Targeted genetic analysis of specific genomic regions was used to assess the accumulation of mutations. Correlation and regression analysis were used to examine the relationship between efficiency of DNA repair and mutation frequency, with the results being adjusted for demographic and exposure related factors.
Results: The individuals who had lower DNA repair activity had a significantly greater amount of mutations than those with efficient repair. The mean DNA repair efficiency was 78.6 ± 8.4% in the high repair group, 51.2 ± 7.9% in the moderate repair group, and 27.8 ± 6.5% in the low repair group (p < 0.001). The frequency of mutations rose with increasing groups (3.2 ± 1.4 mutations/sample for the high repair group to 11.8 ± 3.6 mutations/sample for the low repair group, p< 0.001). We found a high mutational load (mutation burden) was negatively correlated with the efficiency of DNA repair (r = -0.72, p < 0.001).
Conclusion: The results confirm that slower DNA repair is highly correlated with increased number of gene mutations. DNA repair assays may give useful clues on genomic instability and disease susceptibility. To confirm DNA repair efficiency as a possible biomarker for early molecular risk assessment and personalized healthcare strategies, further large-scale longitudinal studies are recommended.
