Bazzaz Javad Tavakkoly, Amoli Mahsa M, Pravica Vera, Chandrasecaran Ramesh, Boulton Andrew J, Larijani Bagher, Hutchinson Ian V
Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Ophthalmic Genet. 2010 Sep;31(3):103-7. doi: 10.3109/13816810.2010.482553.
Nitric oxide (NO) is a major mediator in vascular biology, regulating blood pressure and regional blood flow. NO and the enzymes required for its production may contribute to the aetiology of vascular pathologies. In diabetes, over-production of NO might play a role in the development of diabetic nephropathy, while reduced NO production may be related to the development of diabetic retinopathy and neuropathy, where VEGF (vascular endothelial growth factor) levels are increased in a counter regulatory manner. Among the three nitric oxide synthase (NOS) enzymes most attention has focussed on endothelial NOS (eNOS) because of its relevance to angiopathies.
In this study the influence of a single nucleotide polymorphism at position -786 in the eNOS gene, where there is a C/T base substitution, on development of type 1 diabetes mellitus (T1DM) and its microvascular complications was studied in 249 British Caucasian type 1 diabetics using a case-control association design. Genotyping was carried out using PCR-RFLP technique.
There was a significant association between the polymorphism -786*C/T and both T1DM and diabetic retinopathy. The distribution of eNOS gene polymorphism genotype frequencies showed a significant difference observed between diabetic patients and healthy controls [CC+CT vs. TT p = 0.05, OR = 1.5 95%CI(0.9-2.5)]. The genotype frequencies for eNOS gene polymorphism was also significantly different between diabetic retinopaths and healthy controls [CC+CT vs. TT p = 0.0000 OR = 3.4 95%CI(1.9-6.1) No significant differences for eNOS allele and genotype frequencies were found in other groups compared to the controls.
Therefore, eNOS gene variation may be a factor in the genetic propensity to T1DM and diabetic retinopathy that may have a prognostic value or may suggest interventional approaches to regulate eNOS in patients with diabetes.
一氧化氮（NO）是血管生物学中的主要介质，可调节血压和局部血流。NO及其产生所需的酶可能与血管病变的病因有关。在糖尿病中，NO的过度产生可能在糖尿病肾病的发展中起作用，而NO产生减少可能与糖尿病视网膜病变和神经病变的发展有关，在这些病变中血管内皮生长因子（VEGF）水平以反调节方式升高。在三种一氧化氮合酶（NOS）中，由于其与血管病变的相关性，内皮型NOS（eNOS）受到了最多关注。
在本研究中，采用病例对照关联设计，对249名英国白种人1型糖尿病患者进行研究，探讨eNOS基因-786位点（存在C/T碱基替换）的单核苷酸多态性对1型糖尿病（T1DM）及其微血管并发症发生发展的影响。采用PCR-RFLP技术进行基因分型。
-786*C/T多态性与T1DM和糖尿病视网膜病变均存在显著关联。eNOS基因多态性基因型频率分布在糖尿病患者和健康对照之间存在显著差异[CC+CT与TT比较，p = 0.05，OR = 1.5，95%CI（0.9 - 2.5）]。糖尿病视网膜病变患者与健康对照之间eNOS基因多态性的基因型频率也存在显著差异[CC+CT与TT比较，p = 0.0000，OR = 3.4，95%CI（1.9 - 6.1）]。与对照组相比，其他组的eNOS等位基因和基因型频率未发现显著差异。
因此，eNOS基因变异可能是T1DM和糖尿病视网膜病变遗传易感性的一个因素，可能具有预后价值，或可能提示对糖尿病患者调节eNOS的干预方法。
