Rudofsky Gottfried, Schroedter Antonia, Schlotterer Andreas, Voron'ko Olga E, Schlimme Martin, Tafel Joerg, Isermann Berend H, Humpert Per M, Morcos Michael, Bierhaus Angelika, Nawroth Peter P, Hamann Andreas
Division of Endocrinology and Metabolism, Department of Medicine, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Diabetes Care. 2006 Jan;29(1):89-94. doi: 10.2337/diacare.29.01.06.dc05-0757.
We studied the association between polymorphisms in the UCP genes and diabetes complications in patients with type 1 diabetes.
We analyzed 227 patients with type 1 diabetes using PCR and subsequent cleavage by restriction endonucleases for the promoter variants A-3826G in the UCP1 gene, G-866A in the UCP2 gene, and C-55T in the UCP3 gene.
No effect of the A-3826G polymorphism in the UCP1 gene on diabetes complications was found. Patients who were heterozygous or homozygous for the G-866A polymorphism in the UCP2 gene or the C-55T polymorphism in the UCP3 gene had a significantly reduced prevalence of diabetic neuropathy (UCP2: odds ratio 0.44 [95% CI 0.24-0.79], P = 0.007; UCP3: 0.48 [0.25-0.92], P = 0.031), whereas there was no association with other diabetes complications. This effect was stronger when G-866A and C-55T occurred in a cosegregatory manner (UCP2 and UCP3: 0.28 [0.12-0.65], P = 0.002). Furthermore, a multiple logistic regression model showed an age- and diabetes duration-independent effect of the cosegregated polymorphisms on the prevalence of diabetic neuropathy (P = 0.013).
Our data indicate that both the G-866A polymorphism in the UCP2 gene and the C-55T polymorphism in the UCP3 gene are associated with a reduced risk of diabetic neuropathy in type 1 diabetes. Thus, the results presented here support the hypothesis that higher expression of uncoupling protein might prevent mitochondria-mediated neuronal injury and, ultimately, diabetic neuropathy.
我们研究了1型糖尿病患者UCP基因多态性与糖尿病并发症之间的关联。
我们使用聚合酶链反应（PCR）及随后的限制性内切酶切割分析了227例1型糖尿病患者，检测UCP1基因启动子变体A-3826G、UCP2基因的G-866A以及UCP3基因的C-55T。
未发现UCP1基因的A-3826G多态性对糖尿病并发症有影响。UCP2基因G-866A多态性或UCP3基因C-55T多态性的杂合子或纯合子患者，糖尿病神经病变的患病率显著降低（UCP2：比值比0.44 [95%置信区间0.24 - 0.79]，P = 0.007；UCP3：0.48 [0.25 - 0.92]，P = 0.031），而与其他糖尿病并发症无关联。当G-866A和C-55T共分离时，这种效应更强（UCP2和UCP3：0.28 [0.12 - 0.65]，P = 0.002）。此外，多元逻辑回归模型显示，共分离的多态性对糖尿病神经病变患病率具有独立于年龄和糖尿病病程的影响（P = 0.013）。
我们的数据表明，UCP2基因的G-866A多态性和UCP3基因的C-55T多态性均与1型糖尿病患者糖尿病神经病变风险降低相关。因此，本文结果支持解偶联蛋白高表达可能预防线粒体介导的神经元损伤并最终预防糖尿病神经病变这一假说。
