Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage.

Abstract

Genetic variations of the serine proteinase inhibitor family E member 1 (SERPINE1) gene, which encodes plasminogen activator inhibitor 1, correlate with serum levels of its product and are associated with thrombophilia and coronary atherosclerosis. Various SERPINE1 ;gene polymorphisms have been identified. However, only the functional 5G/4G polymorphism has been assessed in the context of aneurysmal subarachnoid hemorrhage (aSAH). We assessed associations of 6 SERPINE1polymorphisms with the clinical sequelae of aSAH. From 2012 to 2015, patients with aSAH were prospectively enrolled into the CARAS (Cerebral Aneurysm Renin Angiotensin System) study at 2 major academic institutions. Blood samples were used to evaluate 6 common SERPINE1 single nucleotide polymorphisms via 5' exonuclease (Taqman) genotyping assays. There was an association of the AA genotype of rs2227631 with the 4G/4G genotype and of the GG genotype of rs7242 with the AA genotype of rs2227684. In multivariable analysis, patients with the AA genotype of rs2227631 and 4G/4G genotype had an increased risk for developing delayed cerebral ischemia. Patients with the GG genotype of rs7242 and AA genotype of rs2227684 had a decreased risk for a poor functional outcome. SERPINE1 gene polymorphisms were associated with delayed cerebral ischemia and functional outcome after aSAH. These associations may arise from alterations of plasminogen activator inhibitor 1 levels.