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

• Main Authors: Katko M, Galgoczi E, Erdei A, Gazdag A, Berta E, Bodor M, Seres I, Hircsu I, Badics A, Ujhelyi B, Sira L, Bhattoa HP, Nagy EV
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-05-01
• Series: Journal of Inflammation Research
• Subjects: thyroid eye disease; graves’ disease; pai-1; 4g/5g polymorphism; risk factor
• Online Access: https://www.dovepress.com/the-4g5g-polymorphism-of-plasminogen-activator-inhibitor-type-1-is-a-p-peer-reviewed-fulltext-article-JIR

Monika Katko,1 Erika Galgoczi,1 Annamaria Erdei,1 Annamaria Gazdag,1 Eszter Berta,1 Miklos Bodor,1 Ildiko Seres,2 Ildiko Hircsu,1 Arpad Badics,1 Bernadett Ujhelyi,3 Livia Sira,1 Harjit Pal Bhattoa,4 Endre V Nagy1 1Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 2Division of Metabolic Diseases, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 3Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 4Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, HngaryCorrespondence: Endre V NagyDivision of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, Debrecen, 4032, HungaryTel [phone]Email [e-mail]: 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.Keywords: thyroid eye disease, Graves’ disease, PAI-1, 4G/5G polymorphism, risk factor