The effect of DNA repair gene variants on COVID-19 disease: susceptibility, severity, and clinical course

Naci Senkal1, Istemi Serin2, Sacide Pehlivan3

  • 1Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Insights

DNA repair gene variants, specifically XRCC4 rs6869366 and XRCC1 rs25487, are linked to COVID-19 susceptibility and disease severity. This study highlights their potential role in the pathogenesis of Coronavirus disease 2019.

Area of Science:

  • Genetics and Molecular Biology
  • Infectious Diseases
  • Genomic Medicine

Background:

  • Oxidative stress contributes to DNA damage and plays a role in Coronavirus disease 2019 (COVID-19) pathogenesis.
  • DNA repair mechanisms are crucial for cellular integrity and may influence susceptibility to viral infections.
  • Genetic variations in DNA repair genes could impact an individual's response to COVID-19.

Purpose of the Study:

  • To investigate the association between specific DNA repair gene variants (XRCC4 rs28360071, rs6869366, and XRCC1 rs25487) and susceptibility to COVID-19 in a Turkish population.
  • To evaluate the impact of these variants on the clinical course and severity of COVID-19.
  • To explore the role of DNA repair gene variants in COVID-19 pathogenesis for the first time.

Main Methods:

  • Genotyping of XRCC4 (rs28360071, rs6869366) and XRCC1 (rs25487) variants using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP).
  • Comparative analysis of genotype and allele frequencies between 200 COVID-19 patients and 100 healthy controls.
  • Correlation of genetic variants with clinical parameters including disease severity, hospitalization, and 28-day follow-up outcomes.

Main Results:

  • The XRCC4 rs6869366 G/G genotype and G allele were significantly more frequent in COVID-19 patients compared to controls.
  • Conversely, XRCC4 rs6869366 G/T and T/T genotypes were more prevalent in the control group.
  • The XRCC1 rs25487 A/A and A/G genotypes showed a significant association with COVID-19 disease.
  • All intensive care unit (ICU) patients carried the XRCC4 rs6869366 G/G genotype.

Conclusions:

  • The DNA repair gene variants XRCC4 rs6869366 and XRCC1 rs25487 are associated with increased susceptibility to COVID-19.
  • These genetic variants may also influence the clinical course and severity of Coronavirus disease 2019.
  • This study provides novel insights into the genetic underpinnings of COVID-19 susceptibility and progression.

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