Impact of PAI-1 4G/5G and C > G polymorphisms in acute ST elevation myocardial infarction and stable angina patients: A single center Egyptian study

Background: Many genetic factors, including polymorphisms in the genes regulating blood coagulation and fibrinolysis have been proposed as risk factors for coronary artery disease (CAD). PAI-1 is the chief inhibitor of tissue plasminogen activator and urokinase plasminogen activator. PAI-1 has a crucial role in regulation of fibrinolysis.Aim of the study: Is to investigate the association between Plasminogen activator inhibitor-1 (PAI-1) 4G/5G, PAI-1C/G polymorphisms and CAD. In addition, studying the relation of these polymorphisms to the level of active PAI-1 in Egyptian patients presenting to a single tertiary center in Cairo.Subjects and methods: One hundred and forty-four patients were included in this study: 42 STEMI (ST elevation myocardial infarction) patients, 63 stable angina patients, and 39 as a control group. Detection of PAI-1 4G/5G and C > G polymorphisms was done using allele specific polymerase chain reaction and restriction fragment length polymorphism (RFLP) respectively. Plasma plasminogen activator inhibitor-1 activity was detected using enzyme linked immunosorbent assay (ELISA).Results: In the studied CAD patients, PAI-14G/5G polymorphism showed 31.7%, and 68.3% for 5G/5G, and (4G/5G + 4G/4G) respectively; however for the control group, 5G/5G, and (4G/5G + 4G/4G) were detected in 21.6%, and 78.4% respectively (p value 0.59). The genotypic frequencies for PAI-1C/G in CAD patients accounted for 27% (CC), 73% (CG + GG); while in the control group these frequencies were 35.3%, and 64.7% respectively (p value 1.43).Conclusion: No significant association between PAI-1 4G/5G and C > G polymorphisms and the risk of coronary artery disease or the activity level of PAI-1 among the studied Egyptian population sample. However, STEMI patients showed significant presence of combined mutant allele of both genes more frequently.Keywords: Coronary artery disease, Plasminogen activator inhibitor, Genetic polymorphism, 4G/5G, C>

FOXO3a gene polymorphism and bronchial asthma in Egyptian children INTRODUCTION Bronchial asthma is the most prevalent chronic immunological disorder in childhood period. It is characterized by airways inflammation and bronchial hyper-responsiveness where

Background: FOXO3a proteins play multiple crucial roles in immune response. FOXO3 inhibits T cell proliferation, induces T cell apoptosis via upregulation of proapoptotic proteins and it suppresses T cell activation preventing autoimmunity. The role of FOXO3a gene in the pathogenesis of bronchial asthma has been studied in few ethnic groups and revealed its implication in asthma pathogenesis.Objectives: The aim of the current study is to detect the association between single nucleotide polymorphism of the FOXO3a gene (rs13217795) and bronchial asthma, atopy and asthma severity in Egyptian children.Methods: The current cross-sectional case-control study was performed on 75 asthmatic children aged 2 to 12 years following up in the pulmonology outpatient clinic in Children's hospital, Cairo University and 75 age and sex matched healthy controls. Candidates were subjected to clinical evaluation in addition to genotyping for the FOXO3a gene polymorphism using PCR-RFLP technique.Results: The highest frequency was for the heterozygous type CT in both cases and controls groups. The genotype frequencies of mutant type TT for cases and controls were 12 % and 16% respectively, and the T allele frequencies were 37.2% in cases and 46.7% in the control group while CC genotype was present in 37.3% of asthmatic patients and 22.6% in the controls and the C allele was detected in 62.8% and 53.3% for cases and controls respectively. No statistically significant differences were observed between asthmatic patients and controls regarding the different genotypes of the FOXO3a gene polymorphism (p=0.161). No significant association was detected between the different genotypes of the FOXO3a gene polymorphism and the atopic status (p=0.536) or the different grades of asthma severity (p= 0.545).Conclusions: The study of FOXO3a gene polymorphism (rs13217795) in asthmatic Egyptian children revealed low frequency of the mutant TT genotype among cases and controls. In the current study, FOXO3a polymorphism has no role in the pathogenesis of asthma or atopy. Moreover, it has no relation to degree of disease severity.Keywords: Asthma, FOXO3a, gene, children, Egyptian, polymorphis

Study of the effect of HFE gene mutations on iron overload in Egyptian thalassemia patients

Background: HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in β-thalassemia patients and carriers remains controversial. Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in β-thalassemia patients and carriers and to investigate its effect on their serum ferritin levels. Patients and methods: A total of 100 β-thalassemia subjects; 75 patients and 25 carriers were screened for HFE gene mutations by PCR-RFLP. Serum ferritin measured by ELISA was evaluated in relation to HFE mutations. Results: Twenty-eight β-thalassemia patients (37.3%) were heterozygotes for H63D mutation (H/D), 8 (10.7%) were D/D and 39 (52%) were negative (H/H). Among carriers, 4 (16%) were D/D and 21 (84%) were H/H homozygotes. C282Y mutant allele was not detected in any of the subjects. Serum ferritin levels were significantly higher in β-thalassemia patients heterozygotes or homozygotes for H63D mutation compared to those without mutation (p = 0.000). Carriers homozygotes for H63D mutation showed significantly higher serum ferritin levels compared to those without mutation (p < 0.001). Conclusion: Homozygosity for H63D mutation tends to be associated with higher ferritin levels in beta-thalassemia patients and carriers suggesting its modulating effect on iron load in these cases