Elevated Expression of Plasminogen Activator Inhibitor (PAI-1/SERPINE1) is Independent from rs1799889 Genotypes in Arthrofibrosis.

ABSTRACT

Arthrofibrosis is characterized by excessive extracellular matrix deposition in patients with total knee arthroplasties (TKAs) and causes undesirable joint stiffness. The pathogenesis of arthrofibrosis remains elusive and currently there are no diagnostic biomarkers for the pathological formation of this connective tissue. Fibrotic soft tissues are known to have elevated levels of plasminogen activator inhibitor-1 (PAI-1) (encoded by SERPINE1), a secreted serine protease inhibitor that moderates extracellular matrix remodeling and tissue homeostasis. The 4G/5G insertion/deletion (rs1799889) is a well-known SERPINE1 polymorphism that directly modulates PAI-1 levels. Homozygous 4G/4G allele carriers typically have higher PAI-1 levels and may predispose patients to soft tissue fibrosis (e.g., liver, lung, and kidney). Here, we examined the genetic contribution of the SERPINE1 rs1799889 polymorphism to musculoskeletal fibrosis in arthrofibrotic (n = 100) and non-arthrofibrotic (n = 100) patients using Sanger Sequencing. Statistical analyses revealed that the allele frequencies of the SERPINE1 rs1799889 polymorphism are similar in arthrofibrotic and non-arthrofibrotic patient cohorts. Because the fibrosis related SERPINE1 rs1799889 polymorphism is independent of arthrofibrosis susceptibility in TKA patients, the possibility arises that fibrosis of joint connective tissues may involve unique genetic determinants distinct from those linked to classical soft tissue fibrosis.