Association between urokinase-plasminogen activator gene T4065C polymorphism and risk of mitral valve prolapse

Background: Abnormalities of collagen and elastic fibers were found in floppy mitral valves (FMV). Urokinase-plasminogen activator (PLAU) was suggested to be involved in the pathogenesis of elastin and collagen degradation in arterial aneurysm. The role of PLAU genetic variant in mitral valve prolapse (MVP) has not been studied. We, therefore, performed a case-controlled study investigating the possible relation between the PLAU gene polymorphisms and risk of MVP in Taiwan Chinese. Methods: We studied 100 patients with MVP diagnosed by echocardiography and 106 age- and sex-matched normal control subjects. The T4065C and T3995C polymorphisms of the PLAU gene were identified by polymerase chain reaction (PCR)-based restriction analysis. Results: There was a significant difference in either the genotype distribution or allelic frequencies between MVP cases and controls for PLAU gene T4065C polymorphism (P=0.0001 and 0.0002, respectively). An odds ratio for risk of MVP associated with PLAU T4065C TC genotype was 6.03 (95% confidence interval 2.11–14.83). An odds ratio for risk of MVP associated with PLAU T4065C T allele was 4.99 (95% confidence interval 1.93–12.91). There was no significant difference in either the genotype distribution or allelic frequencies between MVP cases and controls for PLAU T3995C polymorphism. Further categorization of the MVP patients into mild and severe subgroups revealed no statistical difference between these two subgroups for PLAU T4065C and T3995C polymorphisms. Conclusions: This study shows that patients with MVP have a higher frequency of PLAU T4065C TC genotype and T allele that supports a role of the PLAU T4065C polymorphism in determining the risk of MVP among the Chinese population in Taiwan.