eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy

Taverna, Mariano J.; Sola, Agnès; Guyot-Argenton, C; Pacher, Nathalie; Bruzzo, F.; Chevalier, Alain; Slama, G.; Reach, Gérard; Selam, J. L.

doi:10.1046/j.1464-5491.2002.00681.x

Cited by 54 publications

(40 citation statements)

References 29 publications

(42 reference statements)

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“…Some studies (9,10), but not all (11,12), reported that the "a" allele of the eNOS 27-bp repeat polymorphism was positively associated with DN. In contrast, Taverna et al (13) reported that the "b" allele and the bb genotype were associated with severe DR. Similarly, Frost et al (14) reported that the bb genotype of the 27-bp repeat was associated with DR.…”

Section: Enos Gene and Diabetic Macular Edemamentioning

confidence: 91%

“…Recently, the 27-bp repeat has been found to be associated with the progression of diabetic nephropathy (DN) (9) or advanced DN (10), although some studies did not confirm this association (11,12). Also, the possible association of eNOS polymorphisms with DR has been examined in several studies, and a "b" allele of the 27-bp repeat was associated with a high risk of DR in type 1 diabetes (13,14). In the present study, we examined the eNOS polymorphisms to assess their possible association with DR and maculopathy.…”

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confidence: 99%

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Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

et al. 2004

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OBJECTIVE -We examined the endothelial nitric oxide (eNOS) gene polymorphisms to assess its possible association with diabetic retinopathy and macular edema.RESEARCH DESIGN AND METHODS -A total of 226 patients with type 2 diabetes and 186 healthy subjects were studied. Type 2 diabetic patients consisted of 110 patients without retinopathy, 46 patients with nonproliferative diabetic retinopathy, and 71 patients with proliferative diabetic retinopathy. Diabetic macular edema was present in 48 patients. Three polymorphisms of the eNOS gene were determined: T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7.RESULTS -Close linkage disequilibrium was observed between the T-786C polymorphism and the 27-bp repeat, as has been previously reported, but Glu298Asp was not in linkage disequilibrium with the other two polymorphisms. The eNOS gene polymorphisms were not significantly associated with the presence of retinopathy or with retinopathy severity or type 2 diabetes itself. However, by both association study and multiple logistic regression analysis, the T-786C and 27-bp repeat polymorphisms were significantly associated with a risk of developing macular edema with the Ϫ786C allele and the "a" allele increasing the risk.CONCLUSIONS -The present study suggests that the eNOS gene is a novel genetic risk factor for diabetic macular edema. The eNOS gene polymorphisms may contribute to the development of macular edema by impairing basal eNOS expression and resulting in the breakdown of the blood-retina barrier. Diabetes Care 27:2184 -2190, 2004D iabetic retinopathy (DR) remains the major cause of blindness among adults (1). In addition, diabetic maculopathy or macular edema (ME), which may occur at any stage of DR, is an important cause of visual impairment (1-3). Among the pathophysiological steps involved in the development of ME, the most important mechanism is breakdown of the blood-retina barrier (BRB) (2,3). Both the inner BRB formed by the retinal capillary endothelial cell tight junctions and the outer BRB formed by the retinal pigment epithelial cell tight junctions can be affected during the development of ME.Nitric oxide (NO) is a multifunctional molecule that plays a key role in physiological processes such as the regulation of vascular tone and the antiproliferative effects on vascular smooth muscle cells (4,5). NO is produced by three different isoforms of NO synthase (NOS): endothelial NOS (eNOS), neural NOS, and inducible NOS (iNOS). Although NO produced in large amounts by iNOS is regarded as a toxic, damaging agent, it is suggested that a low concentration of NO produced by constitutively expressed eNOS is necessary to maintain good endothelial function (5). Thus, eNOS appears to present an attractive candidate susceptibility gene for diabetic microvascular complications as well as cardiovascular diseases.Several polymorphisms have been identified in the eNOS gene (NOS3) (6,7). In particular, T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7 have...

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Section: Enos Gene and Diabetic Macular Edemamentioning

confidence: 91%

mentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

et al. 2004

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“…36 Higher total plasma insulin concentration has been reported, [37][38][39] which seems to be genetically predetermined 40 and which is a risk factor for retinopathy. Other reasons may include increased vitamin D deficiency in Asians 41 which has been shown to affect diabetic retinopathy, 42 earlier changes required in treatment in Asians 37 which is considered a risk factor, 43 and heath care access which will invariably affect control, diagnosis, and progression and eventually make an impact on diabetic retinopathy. Precisely how these different risk factors influence diabetic retinopathy in the two races is largely undetermined.…”

Section: Discussionmentioning

confidence: 99%

Impact of age and duration on sight–threatening retinopathy in South Asians and Caucasians attending a diabetic clinic

Pardhan

Gilchrist

Mahomed

2004

Eye

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Aims To examine diabetic retinopathy in Asians and Caucasians attending a hospital diabetic clinic and to evaluate the impact of the significant risk factors on the probability of sight-threatening retinopathy. Methods A total of 500 diabetic patients (268 Asians, 232 Caucasians) who attended a diabetic clinic within a defined time period were examined for severity of diabetic retinopathy. The existence of sight-threatening retinopathy (STR) was compared in the two groups. Significant risk factors such as age, duration and hypertension were analysed against the probability of STR in each of the two races. Results Asians demonstrated significantly higher rates of STR. Univariate analysis showed age, duration, race, gender, and insulin-requiring status to be significantly associated with STR. Multivariate logistic regression showed a significant association of STR with race, age and duration of diabetes, with no significant interaction effects between variables. The logistic regression model predicted STR in Asians to be matched to that in Caucasians by a 12.5-year difference factor; that is, Caucasians were older by 12.5 years or had a 12.5-year longer duration than Asians for the same level of STR. Conclusions After adjusting for age and duration of diabetes, the probability of STR in Asian diabetic patients attending the diabetic clinics in Bradford is significantly higher than that in Caucasians (odds ratio ¼ 3.184, Po0.05). The impact of age and duration was significantly higher in patients of South Asian origin compared to Caucasians.

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“…Bazı çalışmalarda VEGFün 5' kodlanmamış bölgesinde C-634G olarak tanımlanan genel bir polimorfizmin diabetik retinopati mevcudiyeti ile doğrudan ilişkili olduğu ve fonksiyonel olarak önemli olduğu sonucuna varılmıştır. eNOS geninde çeşitli polimorfizmler tanımlanmıştır (14)(15).Tip I DM' da 27-bp tekrarının 'b' alleli yüksek diabetik retinopati riski ile ilişkili bulunmuştur (16,17). (32).…”

Section: Nitrik Oksitin Gen Haritasındaki Lokusu : 7q36unclassified

“…Özellikle promotor bölgesindeki T-786C, 4. intron bölgesinde 27-bp tekrarı ve 7. eksondaki Glu298Asp dikkat çekmiştir. Tip I DM'da 27-bp tekrarının 'b' aleli yüksek diabetik retinopati riski ile ilişkili bulunmuştur (16,17). Tip II DM'lu hasta grubunda eNOS gen polimorfizmi (T-786C, promotor bölgede ve intron 4 deki 27bp tekrarı) makula ödeminin oluşumu ile direkt ilişkili bulunmuştur.…”

Section: Introductionunclassified

Diyabetik Retinopati ve Nitrik Oksit

İnan¹

2015

Kocatepe Tıp Dergisi

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eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy

Abstract: We demonstrate in Caucasians with Type 1 diabetes that (i) eNOS4a/a is associated with absent or non-severe DR, and (ii) eNOS4b/b is associated with severe DR.

Cited by 54 publications

References 29 publications

Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

Impact of age and duration on sight–threatening retinopathy in South Asians and Caucasians attending a diabetic clinic

Diyabetik Retinopati ve Nitrik Oksit

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