The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease.

Introduction: Thyroid eye disease (TED) is an autoimmune disease of the orbits. Once developed, complete cure is rare. Plasminogen activator inhibitor type 1 (PAI-1) contributes to remodeling of connective tissue and has a central role in the pathogenesis of TED. We aimed to test if the 4G/5G polymorphism of PAI-1 is a predictor of the development of moderate-to-severe TED.

Methods: A total of 185 patients with Graves' disease, 87 of them with TED, 98 without TED, as well as 201 healthy controls, were studied. Genomic DNA was isolated from peripheral blood samples. The 4G/5G polymorphism of the PAI-1 gene was analyzed by allele-specific PCR, and the distribution of genotypes was calculated in each group. Plasma PAI-1 and thyroid hormone levels were measured by ELISA and ECLIA, respectively.

Results: The 4G/4G genotype was associated with the development of moderate-to-severe TED (OR = 2.54; 95% CI: 1.26-5.14; p < 0.01). The 4G/5G polymorphism of PAI-1 was not a predictor of plasma PAI-1 levels.

Conclusion: The 4G/4G genotype of PAI-1 is a risk factor for the development of moderate-to-severe TED. Patients with Graves' disease who harbor this genotype may be candidates for special attention towards the development of TED.