ABSTRACT
The COVID-19 pandemic has affected people worldwide with varying clinical presentations ranging from mild to severe or fatal, and studies have found that age, gender, and some comorbidities can influence the severity of the disease. It would be valuable to have genetic markers that might help predict the likely outcome of infection. For this objective, genes encoding VEGFR-2 (rs1870377), CCR5Δ32 (rs333), and TLR3 (rs5743313) were analyzed for polymorphisms in the peripheral blood of 160 COVID-19 patients before COVID-19 vaccine was available in Türkiye. We observed that possession of the VEGFR-2 rs1870377 mutant allele increased the risk of severe/moderate disease in females and subjects ≥65 years of age, but was protective in males <65 years of age. Other significant results were that the CCR5Δ32 allele was protective against severe disease in subjects ≥65 years of age, while TLR3 rs5743313 polymorphism was found to be protective against severe/moderate illness in males <65 years of age. The VEGFR-2 rs1870377 mutant allele was a risk factor for severe/moderate disease, particularly in females over the age of 65. These findings suggest that genetic polymorphisms have an age- and sex-dependent influence on the severity of COVID-19, and the VEGFR-2 rs1870377 mutant allele could be a potential predictor of disease severity.
Subject(s)
COVID-19 , Polymorphism, Single Nucleotide , Aged , Female , Humans , Male , COVID-19/genetics , COVID-19 Vaccines , Disease Progression , Genetic Predisposition to Disease , Pandemics , Toll-Like Receptor 3 , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
BACKGROUND: The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. METHODS: Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. RESULTS: All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176) in the breast cancer patients, and 14% (28/200) in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02). CONCLUSION: Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05) computed in this study suggest that H63D has a positive association with breast cancer.
Subject(s)
Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Histocompatibility Antigens Class I/genetics , Membrane Proteins/genetics , Mutation , Adult , Aged , Breast Neoplasms/metabolism , Case-Control Studies , DNA/chemistry , DNA Mutational Analysis , DNA Restriction Enzymes/metabolism , Female , Hemochromatosis Protein , Heterozygote , Homozygote , Humans , Middle Aged , Models, Statistical , Molecular Weight , Odds Ratio , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , TurkeyABSTRACT
OBJECTIVE: Coronary artery disease (CAD) is a common, complex, and progressive disorder characterized by the accumulation of lipids and fibrous elements in the arteries. It is one of the leading causes of death in industrialized nations. Oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays an important role in the initiation and progression of atherosclerosis. Paraoxonase1 (PON1) is involved in lipid metabolism and is believed to protect LDL oxidation. In our study, we aimed to clarify the relationship between PON1 gene L55M polymorphism and the extent and severity of CAD. METHODS: In total, 114 patients (54 males, mean age: 56.7 ± 12.0 years; 60 females, mean age: 55.7 ± 13.2 years) with stable angina or angina equivalent symptoms were enrolled in this prospective study. Cardiological evaluation was performed with electrocardiogram and transthoracic echocardiogram. The presence of hypertension, dyslipidemia, diabetes, and smoking status were ascertained. The patients were grouped according to their Gensini scores and gender. Genetic analysis of the PON1 gene L55M polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We determined that the LL genotype was more prevalent in patients with Gensini score higher than or equal to 20 (p=0.026) and that this correlated with severe atherosclerotic coronary artery lesions in both gender groups, reaching a statistical significance in the female subjects (p=0.038). CONCLUSION: It was thought that the PON1 gene L55M polymorphism plays a significant role in CAD progression, especially in females.