4G/4G PAI-1 gene variant in a patient with non-healing ulcers

Abstract

Plasminogen activator inhibitor is a serine protease inhibitor from the serpin gene family that modulates fibrin clot breakdown.PAI-1 irreversibly inhibits tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) from activatingplasminogen. PAI-1 also inhibits integrin-vitronectin and vitronectin-vitronectin interactions that are essential for cell migration,adhesion, and angiogenesis. We describe a patient, who developed chronic non-healing ulcers after minimal trauma to severalareas of his body. Genetic testing revealed the 4G/4G homozygous genotype for the polymorphism in the promoter regionof the PAI-1 gene. Increased PAI-1 activity prevents the breakdown of the fibrin clot and cell migration to remodel damagedtissue. A combination of poor clot fibrinolysis and cell recruitment to the site of injury may explain our patient’s non-healingulcers following minor traumatic injury. Early treatment with excision and skin grafting may benefit patients presenting withnon-healing ulcers and the homozygous 4G/4G PAI-1 variant. To our knowledge, there have been no reports in the literatureassociating PAI-1 overexpression and chronic non-healing wounds.