Plasminogen Activator inhibitor 1 4G 5G Polymorphism in Hypertension Patients and an in silico approach towards the Prediction of Cancer

Abstract

newline Hypertension, commonly known as high blood pressure, is a widespread cardiovascular condition characterized by persistently elevated arterial pressure and often referred to as a quotsilent killerquot due to its asymptomatic early phase. Essential hypertension, accounting for 90-95% of cases, arises from a complex interplay of genetic, environmental, and lifestyle factors, while secondary hypertension is linked to identifiable medical causes. The prevalence of hypertension is significantly rising globally and in India, with only a small fraction of patients achieving effective blood pressure control. newlineThis study investigates the genetic association between hypertension and the insertion-deletion polymorphism (4G/5G) in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene, which modulates fibrinolysis and blood clot regulation. The 4G allele is linked to higher PAI-1 expression and protein levels, potentially contributing to abnormal fibrinolysis, impaired endothelial function, increased blood clot formation, and consequently, elevated blood pressure newlineThrough a comprehensive multi-step approach involving ELISA to measure circulating PAI-1 levels and ARMS-PCR for genotyping in a North Indian cohort, the study finds that hypertensive patients exhibit significantly higher serum PAI-1 levels compared to controls. The 4G/4G genotype (TT) showed the highest PAI-1 concentrations and was more prevalent among hypertensive individuals, indicating a potential genetic predisposition to hypertension associated with this polymorphism. An in-silico analysis also suggests a correlation between PAI-1 polymorphism and increased risk of certain cancers. newlineThese findings elucidate the role of PAI-1 4G/5G polymorphism in hypertension pathogenesis and highlight its significance in personalized medical interventions aimed at cardiovascular health risk reduction. Further research with larger sample sizes is recommended to strengthen these conclusions. newline