Role of angiotensin-converting enzyme insertion/deletion and plasminogen activator inhibitor-1 4G/5G gene polymorphisms in retinal vein occlusion

Abstract

Retinal vein occlusion (RVO) is one of the leading causes for a severe visual loss in patients older than 60 years. Hypofibrinolysis because of increased plasminogen activator inhibitor-1 (PAI-1) plasma concentrations has been identified as a risk factor [1][2][3]. Yet only very limited and at least partly conflicting data on the role of gene polymorphism known to affect PAI-1 plasma levels are available [2][3][4]. Recently, Gori et al. [2] investigating 112 patients with RVO suggested both homozygosity for the angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism and the combined presence of the PAI-1 4G/4G and ACE DD genotypes as novel risk factors.Homozygosity for the PAI-1 4G/5G gene polymorphism itself was not associated with an increased risk for RVO [2]. No significant difference in the PAI-1 4G/5G genotype distribution was also found in another study including 72 patients with either retinal artery or vein occlusion [4]. These findings, however, are in contrast to Glueck et al. [3], who observed a significantly higher prevalence of the PAI-1 4G-allele among 17 patients with RVO.In the present study genotyping for the ACE I/D and PAI-1 4G/5G gene polymorphisms was performed in 556 patients with RVO (308 females and 248 males) and 322 control subjects (186 females and 136 males). Because of second eye involvement, branch retinal vein occlusion (BRVO) was diagnosed in 348 eyes, and 235 eyes were affected by central retinal vein occlusion (CRVO). Control subjects were recruited from the same geographical area and were seen at the Department of Ophthalmology for other reasons than retinal vascular occlusion. Genomic DNA was isolated from venous blood by standard methods and stored at )20°C. Genotyping for the ACE polymorphism was carried out by size-analysis of polymerase chain reaction products [5], and the PAI-1 4G/5G polymorphism was determined as described by Margaglione et al. [6].The mean age of patients was 67.3 ± 12.7 years (range: 17.5-92.9 years) and 70.2 ± 11.7 years (range: 24.1-91.1 years) in control subjects. As expected, arterial hypertension, hypercholesterolemia and ever-smoking status were found significantly more often among patients with RVO.Genotype distribution and allelic frequencies of the ACE I/D and the PAI-1 4G/5G gene polymorphisms are shown in Table 1. Genotype frequencies of both polymorphisms were in line with those predicted by the Hardy-Weinberg equilibrium, and were similar to those previously reported by other investigators [7,8]. In contrast to the findings of Gori et al.[2], neither the prevalence of the ACE DD genotype nor the ACE D-allele frequency were significantly higher in patients with RVO than among control subjects. In a multivariate logistic regression analysis homozygosity for the ACE D-allele was associated with a non-significant odds ratio of 0.76 (95% CI: 0.52-1.11; P ¼ 0.159) for RVO. Separate analysis of patients with CRVO and BRVO revealed similar results (data not shown), suggesting that the ACE I/D polymorphism is not a major risk facto...

Relationship between angiotensin I-converting enzyme insertion/deletion gene polymorphism and retinal vein occlusion

“…In addition Glueck et al [14] demonstrated that factor V mutation, high levels of heritable factor VIII, high homocysteine levels and low levels of antithrombin III are associated with CRVO as a familial thrombophlia. There were studies reporting findings those are opposite to our study results [30]. Furthermore in a recent study an association among RVO and ACE gen polymorphism was not demonstrated [31].…”

Genetic Background of a Recurrent Unusual Combined Form of Retinal Vein Occlusion: A Case Report

“…PAI-1 activity was determined by the PAI-1 4G/5G polymorphism by polymerase chain reaction and restriction length fragment polymorphism. In another study, Mattes et al [ 12 ] found that among all patients with RVO, 54.5% had the PAI-1 4G/5G gene polymorphism. Conversely, for the angiotensin-converting enzyme (ins/del) and PAI-1 (4G/5G) mutations, no difference was observed between the genotypes of patients with RVO and those of control participants in the study by Russo et al [ 13 ] and Kuhli-Hattenbach et al [ 14 ].…”

Retinal Vein Occlusion and Polymorphisms

“…Gori ve arkadaş-ları, RVT olan hastalarda homozigotik anjiotensin konverting enzim (AKE) insersiyon/delesyon için, (PAI-1 4G/4G ve AKE DD) genotiplerinin bir risk faktörü olduğunu ileri sürmüşlerdir [18]. Ancak Mattes ve arkadaşları ise AKE DD genotipini RVT olan hastalarda önceki yayınla tersi şekilde yüksek bulamamışlar [19]. Trombofilik, gen polimorfizmleri ve RVDT riskini araştıran çalış-mada; faktör V R506Q (faktör V Leiden), protrombin 20210G>A, fibrinojen beta -455G> A, faktör XII (FXII) 46C>T, ve ITGA2 807C>T (platelet glikoprotein Ia [GPIa] 807C>T) ve ITGB3 L59P (platelet GPIIIa PlA1/PlA2) polimorfizmleri çalışılmış ve bu ça-lışma sonunda RVDT olan hastalar ve kontrol grubu arasında risk açısından fark bulamamışlardır [15].…”