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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

Anna Maria Gori
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
,
Rossella Marcucci
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
,
Cinzia Fatini
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
,
Francesca Gensini
3   Department of Clinical Pathophysiology, Unit of Medical Genetics, University of Florence, Florence, Italy
,
Elena Sticchi
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
3   Department of Clinical Pathophysiology, Unit of Medical Genetics, University of Florence, Florence, Italy
,
Andrea Sodi
2   Clinica Oculistica, University of Florence, Florence, Italy
,
Stefania Cappelli
2   Clinica Oculistica, University of Florence, Florence, Italy
,
Ugo Menchini
2   Clinica Oculistica, University of Florence, Florence, Italy
,
Gian Franco Gensini
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
,
Rosanna Abbate
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
,
Domenico Prisco
1   Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Florence, Italy
› Author Affiliations
Further Information

Publication History

Received 07 August 2003

Accepted after resubmission 12 April 2004

Publication Date:
29 November 2017 (online)

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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
 

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