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.
Subject(s)
COVID-19 , DNA-Binding Proteins , Male , Humans , Female , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , COVID-19/genetics , Genotype , Gene Frequency , DNA Repair/genetics , Disease Progression , Polymorphism, Single Nucleotide , Case-Control Studies , X-ray Repair Cross Complementing Protein 1/geneticsABSTRACT
For COVID-19 (Coronavirus Disease-2019) cases, detecting host-based factors that predispose to infection is a very important research area. In this study, the aim is to investigate the MBL2 and NOS3 gene polymorphisms in COVID-19 patients with lung involvement, whose first nasopharyngeal PCR results were negative. Seventy-nine patients diagnosed with COVID-19 between April-June 2020 who were admitted to a university hospital, and 100 healthy controls were included. In the first statistical analysis performed between PCR-positive, CT-negative and PCR-negative, CT-positive patients; the AB of MBL2 genotype was significantly higher in the first group (p = 0.049). The B allele was also significantly higher in the same subgroup (p = 0.001). The absence of the AB genotype was found to increase the risk of CT positivity by 6.9 times. The AB genotype of MBL2 was higher in healthy controls (p = 0.006). The absence of the AB genotype was found to increase the risk of CT positivity; also, it can be used for early detection and isolation of patients with typical lung involvement who had enough viral loads, but whose initial PCR results were negative.
Subject(s)
COVID-19 , Mannose-Binding Lectin , COVID-19/diagnosis , Genetic Predisposition to Disease , Genotype , Humans , Mannose-Binding Lectin/genetics , Nitric Oxide Synthase Type III/genetics , Polymerase Chain Reaction/methodsABSTRACT
BACKGROUND/OBJECTIVES: COVID-19 followed a mortal course in some young patients without any underlying factors, however, it followed a very benign course in some very older individuals with multiple comorbidities. These observations question if some genetic factors may be related to the vulnerability and poor prognosis of the disease. In this study, we aimed to investigate whether MBL2 gene B variant at codon 54 (rs1800450) were related to the variabilities in clinical course of this infection. METHODS: 284 PCR-confirmed COVID-19 patients and 100 healthy controls were included in the study. COVID-19 patients were subdivided according to the clinical features and clinical characteristics were analyzed. DNAs of all patients and controls were examined for the codon 54 A/B (gly54asp: rs1800450) variation in exon 1 of the MBL2 gene. RESULTS: In univariate analysis, BB genotype of MBL2 gene was more common among COVID-19 cases compared with controls (10.9% vs 1.0%, respectively; OR = 12.1, 95%CI = 1.6-90.1, p = 0.001). Multivariate analyses, adjusted for age, sex and MBL genetic variants, revealed that when compared with the COVID-19 patients that had AA genotype (reference), the patients that had BB or AB genotypes suffered from a higher risk for severe disease (for BB genotype, odds ratio (OR) = 5.3, p < 0.001; for AB genotype, OR = 2.9, p = 0.001) and for ICU need (for BB genotype, OR = 19.6, p < 0.001; for AB genotype, OR = 6.9, p = 0.001). On the other hand, there was not any significant difference between the genotype variants in terms of mortality at 28 days or development of secondary bacterial infection. CONCLUSION: The B variants of MBL2 gene at codon 54, which were associated with lower MBL2 levels, were related to a higher risk for a more severe clinical course of COVID-19 infection in some respects. Our findings may have potential future implications, e.g. for use of MBL protein as potential therapeutics or prioritize the individuals with B variants during vaccination strategies.