Associations Among Fibrinogen Polymorphisms -455G/A and - 148C/T, Plasma Levels of The Protein and Coronary Disease in Northern Palestine رسالة ماجستير

Abstract

Background: The primary cause of death for those over 35 in developed nations is coronary disease (CD). Avoiding CD and the mortality associated with it has been viewed as a concern in every country. Fibrinogen (Factor I) is a glycoprotein, which participates in coagulation cascade. According to large sample prospective research, the amount of plasma fibrinogen can independently predict the development of coronary disease. Two single nucleotide polymorphisms in the beta-fibrinogen gene's promoter region (G/A-455, C/T-148) have been linked to elevated concentrations of this protein, and a number of articles have revealed their links with acute cardiovascular events. Objectives: The current research aims to investigate the associations among 455G/A, 148C/T fibrinogen polymorphisms and coronary disease (CD) including unstable coronary disease (UCD) and stable coronary disease (SCD), as well as their relationship to major adverse cardiovascular events (MACE) in a group of Northern Palestine. Methodology: This is a multi-center, prospective control design with a follow-up study of six months. A total of 100 patients with coronary disease (CD), including 41 UCD and 59 SCD were recruited in order to ascertain the relationships between major cardiovascular adverse events (MACE), levels of plasma fibrinogen, and fibrinogen gene polymorphisms in a population of Northern Palestine. Sedentarism, gender, age, and the body mass index were all matched for the groups, which included 70 control subjects. The level of plasma fibrinogen was determined by the von Clauss method. DNA was extracted out of buffy coat and the β-fibrinogen gene polymorphisms (G/A-455, C/T-148) were analyzed by means of PCR-RFLP. Results: The concentrations of plasma fibrinogen, polymorphisms of the fibrinogen gene (455G/A and -148C/T) were compared in all groups. Patients with coronary disease had substantial amounts of plasma fibrinogen (>465 mg/dl). An increase in fibrinogen plasma concentration above 450 mg/dl was linked to cardiovascular death within the group with unstable coronary disease during follow-up study (p = 0.03). Plasma high levels of fibrinogen proteins were associated with the allelic loads of -455G/A genotype and -148C/T (p < 0.005 and p = 0.041, respectively) and with coronary disease (p = 0.021 and p < 0.004, respectively). The -148T allele's genetic load was linked to significant unfavorable cardiovascular events, according to the investigation of subsequent events following an acute coronary event (RR = 1.6, 95% CI = 1.13 - 3.42, p = 0.03). Conclusion: The results of this study provide crucial insight into the connections among plasma fibrinogen levels, fibrinogen polymorphisms (-455G/A, -148C/T), and cardiovascular disease in Northern Palestine. MACE and cardiovascular disease are associated with plasmatic fibrinogen levels above 450 mg/dl and fibrinogen gene polymorphisms (-455G/A and 148C/T). According to this study, cardiovascular risk is linked to these gene variations.