Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels

Anna Maria Gori; Rossella Marcucci; Cinzia Fatini; Francesca Gensini; Elena Sticchi; Andrea Sodi; Stefania Cappelli; Ugo Menchini; Gian Franco Gensini; Rosanna Abbate; Domenico Prisco

doi:10.1160/TH03-08-0509

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(01): 54-60
DOI: 10.1160/TH03-08-0509

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels

Authors

Anna Maria Gori

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
Rossella Marcucci

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
Cinzia Fatini

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
Francesca Gensini

³Department of Clinical Pathophysiology, Unit of Medical Genetics, University of Florence, Florence, Italy
Elena Sticchi

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy

³Department of Clinical Pathophysiology, Unit of Medical Genetics, University of Florence, Florence, Italy
Andrea Sodi

²Clinica Oculistica, University of Florence, Florence, Italy
Stefania Cappelli

²Clinica Oculistica, University of Florence, Florence, Italy
Ugo Menchini

²Clinica Oculistica, University of Florence, Florence, Italy
Gian Franco Gensini

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
Rosanna Abbate

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
Domenico Prisco

¹Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy

Abstract

Summary

Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18–83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20–84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95th percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70–14.30; p = 0.003).The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.013.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89–12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hypertension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.1857.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.

Keywords

Retinal vein occlusion - plasminogen activator inhibitor-1 (PAI-1) - angiotensin converting enzyme (ACE) - genetic polymorphisms - risk factors

Full Text

References

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