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
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DOI：
10.2337/diacare.27.9.2184
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发表时间：
2004-09-01
期刊：
影响因子：
16.2
通讯作者：
Katayama, S
中科院分区：
文献类型：
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作者：
Awata, T;Neda, T;Katayama, S
目的-我们研究了内皮型一氧化氮（eNOS）基因多态性，以评估其可能与糖尿病视网膜病变和黄斑水肿。研究设计和方法-共226例2型糖尿病患者和186名健康受试者进行了研究。2型糖尿病患者包括110例无视网膜病变的患者，46例非增殖性糖尿病视网膜病变患者和71例增殖性糖尿病视网膜病变患者。糖尿病性黄斑水肿48例。eNOS基因启动子区的T-786 C多态性、内含子4的27-bp重复序列多态性和外显子7的Glu 298 Asp多态性。结果T-786 C多态性与27-bp重复序列多态性之间存在连锁不平衡，而Glu 298 Asp与其他两个多态性之间不存在连锁不平衡。eNOS基因多态性与视网膜病变的存在或视网膜病变的严重程度或2型糖尿病本身无显著相关性。然而，通过相关性研究和多元Logistic回归分析，T-786 C和27 bp重复多态性与发展黄斑水肿的风险显着相关，-786C等位基因和“a”等位基因增加风险。结论-本研究表明，eNOS基因是糖尿病黄斑水肿的一个新的遗传危险因素。eNOS基因多态性可能通过损害基础eNOS表达并导致血-视网膜屏障的破坏而促进黄斑水肿的发展。
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 -786C 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.