The Association between Genetic Variations in the PAI-1 Promoter Sequence and the Susceptibility to Acute Cardiac Infarction and Stable Angina. رسالة ماجستير

Abstract

Cardiovascular diseases, such as Acute Cardiac Infarction and Chronic Stable Angina, cause illness and death globally, including in Palestine. Plasminogen activator inhibitor-1 (PAI-1) contributes to regulating the process of breaking down blood clots. Elevated levels of PAI-1 are linked with an increased risk of cardiovascular disease due to blood clots. Genetic variations in the promoter region of the PAI-1 gene, specifically the -675 4G/5G and -844 G/A polymorphisms, may affect the production of PAI-1 and an individual's risk of cardiovascular disease. Despite this, the effect of these genetic variations in the Palestinians remains poorly understood. This study evaluates the presence of the -675 4G/5G (rs1799889) and the -844G/A (rs2227631) variants in the PAI-1 gene and their possible association with Acute Cardiac Infarction or Chronic Stable Angina in patients from Northern Palestine. A case-control study design was employed; each of the three study groups—Acute Cardiac Infarction, Chronic Stable Angina, and healthy controls matched for age and sex—had 50 participants. Clinical and demographic data were collected using structured questionnaires over a one-year period from the Palestinian National Health System, An-Najah National Hospital, and Al-Razi Hospital. Genomic DNA was isolated from whole blood, allele specific polymerase chain reaction (AS-PCR) was used for -675 4G/5G genotyping, and PCR followed by restriction fragment length polymorphism (RFLP) analysis was used to assess - 844G/A. Patients with Acute Cardiac Infarction and Chronic Stable Angina were significantly more likely than healthy controls to have the -675 4G and -844 A alleles. Acute cardiac infarction was more common in carriers of at least one 4G or A allele. These genetic differences increase vulnerability to cardiac disease in Palestine, along with typical risk factors including diabetes, hypertension, smoking, and family history of coronary artery disease. In conclusion, the PAI-1 -675 4G/5G and -844 G/A promoter polymorphisms are connected to a higher incidence of coronary artery disease in Palestinians. To establish their clinical importance, larger investigations using plasma PAI-1 values are advised.