Association between 4G/4G plasminogen activator inhibitor-1 polymorphism, PAI-1 activity, and diabetic retinopathy

Background: Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolysis; however, the relationship between PAI-1 and the most common diabetic microvascular complication, retinopathy, is unclear. Objectives: To examine the association between the 4G/4G polymorphism of the PAI-1 gene with diabetic retinopathy (DR) as well as with the plasma levels of the PAI-1 enzyme among Egyptian patients. Participants and methods: Thirty-three patients who had type 2 diabetes for more than 10 years were compared with 63 patients with proliferative diabetic retinopathy (PDR). Both groups were compared with 48 control individuals. All groups were matched for age and sex. PAI-1 4G/5G genotyping was carried out by a PCR and the PAI-1 levels were measured by enzyme-linked immunosorbent assay testing. Results: Higher plasma PAI-1 activity was associated with a higher risk of DR. The overall frequency of the 4G allele was 54.54% among type 2 diabetes patients versus 78.79% among PDR patients (P 0.01). Using multivariate logistic regression analyses, patients with PDR had a higher representation of the genotype 4G/4G (P 0.05, odds ratio: 3.15, 95% confidence interval 0.13–0.89) and the 4G/4G patients studied had higher plasma levels of PAI-1 activity. Conclusion: The PAI-1 gene polymorphism 4G/4G contributed to the genetic susceptibility to DR and a higher PAI-1 plasma level was independently associated with a higher risk of retinopathy among Egyptians.