Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus
Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus
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DOI：
10.1111/j.1365-2265.2009.03684.x
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发表时间：
2010-05-01
影响因子：
3.2
通讯作者：
Canani, Luis H.
中科院分区：
文献类型：
--
作者：
Crispim, Daisy;Fagundes, Nelson J. R.;Canani, Luis H.
背景与目的解偶联蛋白2 （uncoupling protein 2, UCP2）在线粒体产生活性氧（reactive oxygen species， ROS）过程中起调控作用。由于ROS过量产生与糖尿病视网膜病变（DR）有关，UCP2基因多态性可能参与了这一并发症的发生。我们研究了UCP2基因的-866G/A （rs659366）、Ala55Val （rs660339）和45bp插入/缺失（Ins/Del）多态性是否与增殖性DR （PDR）相关。设计与方法在本病例对照研究中，我们分析了501例2型糖尿病患者（242例有PDR， 259例无任何程度DR）和196例1型糖尿病患者（85例有PDR， 111例无DR）。利用贝叶斯统计方法推断3种UCP2多态性组合构建的单倍型。结果在2型糖尿病组中，多因素分析证实单倍型[A - Val - Ins]是PDR的独立危险因素[校正优势比(aOR) = 2中心点12；P = 0中心点006]，至少一个（aOR = 2中心点75；P = 0中心点00001），或两个副本（aOR = 5中心点30；P = 0中心点00001），表明遗传是加性模型。然而，在1型糖尿病患者中，这种单倍型与PDR的关联只有在至少一个拷贝（aOR = 2中心点68；P = 0中心点014）或两个拷贝（aOR = 6中心点02；P = 0中心点005）存在时才能得到证实。结论单倍型是2型和1型糖尿病患者PDR的重要危险因素。
P>Background and objectiveUncoupling protein 2 (UCP2) plays a role in controlling reactive oxygen species (ROS) production by mitochondria. As ROS overproduction is related to diabetic retinopathy (DR), UCP2 gene polymorphisms might be involved in the development of this complication. We investigated whether the -866G/A (rs659366), Ala55Val (rs660339) and 45 bp insertion/deletion (Ins/Del) polymorphisms in the UCP2 gene might be associated with proliferative DR (PDR).Design and methodsIn this case-control study, we analysed 501 type 2 diabetic patients (242 patients with PDR and 259 subjects without any degree of DR) and 196 type 1 diabetic patients (85 cases with PDR and 111 without DR). Haplotypes constructed from the combination of the three UCP2 polymorphisms were inferred using a Bayesian statistical method.ResultsIn the type 2 diabetic group, multivariate analyses confirmed that the haplotype [A Val Ins] was an independent risk factor for PDR when present in one [adjusted odds ratio (aOR) = 2 center dot 12; P = 0 center dot 006], at least one (aOR = 2 center dot 75; P = 0 center dot 00001), or two copies (aOR = 5 center dot 30; P = 0 center dot 00001), suggesting an additive model of inheritance. Nevertheless, in type 1 diabetic patients, the association of this haplotype with PDR was confirmed only when it was present in at least one (aOR = 2 center dot 68; P = 0 center dot 014) or two copies (aOR = 6 center dot 02; P = 0 center dot 005).ConclusionsThe haplotype [A Val Ins] seems to be an important risk factor associated with PDR in both type 2 and 1 diabetic groups.