Rittig K, Holder K, Stock J, Tschritter O, Peter A, Stefan N, Fritsche A, Machicao F, Häring H-U, Balletshofer B
Department of Endocrinology and Diabetes, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
Horm Metab Res. 2008 Jan;40(1):13-7. doi: 10.1055/s-2007-1004527. Epub 2007 Dec 20.
Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.
胰岛素抵抗和血管疾病都具有相关的遗传背景，受到这些疾病阳性家族史的影响。另一方面，胰岛素抵抗与一氧化氮依赖性血管舒张中的促动脉粥样硬化紊乱有关，这可能促成了这两种疾病之间的联系。我们在参与图宾根生活方式干预项目（TULIP）的200名胰岛素抵抗受试者中，研究了一氧化氮依赖性血管舒张（用13兆赫高分辨率超声测量）与三种相关的一氧化氮合酶（eNOS）多态性之间的关联。这项研究表明，与野生型携带者相比，eNOS内含子4多态性的携带者（aa 2.16%；ab 24.2%；bb 73.2%）的内皮功能明显更差，从而导致eNOS依赖性血管舒张功能更差（p = 0.03，多因素方差分析）。5'非翻译区T - 786C和G894T多态性对eNOS活性没有任何影响。在患2型糖尿病风险增加的受试者中，eNOS内含子4多态性与内皮功能独立相关，这表现为内皮一氧化氮生成紊乱。由于该多态性的高患病率和相对较强的作用，它可能有助于识别与超重和胰岛素抵抗相关的动脉粥样硬化风险增加的受试者。
