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Published on: March 31, 2022
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.
Abstract:
Oxidative stress (OS), which leads to DNA damage, plays a role in the pathogenesis of Coronavirus disease 2019 (COVID-19). We aimed to evaluate the role of DNA repair gene variants [X-ray repair cross complementing 4 (XRCC4) rs28360071, rs6869366, and X-ray cross-complementary gene 1 (XRCC1) rs25487] in susceptibility to COVID-19 in a Turkish population. We also evaluated its effect on the clinical course of the disease. A total of 300 subjects, including 200 COVID-19 patients and 100 healthy controls, were included in this study. These variants were genotyped using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) methods. The patients were divided into three groups: those with a mild or severe infection; those who died or lived at the 28-day follow-up; those who required inpatient treatment or intensive care. There were 87 women (43.5%) and 113 men (56.5%) in the patient group. Hypertension was the most common comorbidity (26%). In the patient group, XRCC4 rs6869366 G/G genotype and G allele frequency were increased compared to controls, while XRCC4 rs6869366 G/T and T/T genotype frequencies were found to be higher in controls compared to patients. For XRCC1 rs25487, the A/A and A/G genotypes were significantly associated with COVID-19 disease. All of the patients hospitalized in the intensive care unit had the XRCC4 rs6869366 G/G genotype. In this study, we evaluated for the first time the impact of DNA repair gene variants on COVID-19 susceptibility. Results suggested that XRCC4 rs6869366 and XRCC1 rs25487 were associated with COVID-19 suspectibility and clinical course.
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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