Polymorphism of the transforming growth factor-beta 1 gene correlates with the development of coronary vasculopathy following cardiac transplantation
Polymorphism of the transforming growth factor-beta 1 gene correlates with the development of coronary vasculopathy following cardiac transplantation
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DOI：
10.1016/s1053-2498(00)00114-5
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发表时间：
2000-06-01
影响因子：
8.9
通讯作者：
Brooks, NH
中科院分区：
文献类型：
--
作者：
Densem, CG;Hutchinson, IV;Brooks, NH
背景资料：转化生长因子-β 1（TGF-β 1）的表达由于其对平滑肌细胞、单核细胞/巨噬细胞、白细胞和细胞外基质积累和增殖的作用而对血管修复至关重要。TGF-β 1基因+915位点的遗传多态性决定了损伤后细胞因子产生的程度。我们研究了心脏移植相关的冠状动脉血管病变（CV）的发展，这种等位基因的变化：使用序列特异性引物的TGF-β 1基因的兴趣区域，聚合酶链反应（PCR）和凝胶电泳确定的基因型在129个心脏移植受者。高（GG）或低/中间生产（CC/GC）基因型的存在和冠状动脉血管造影诊断的冠状动脉vasculopathy的发展之间的关联寻求：C等位基因携带者占10.9%的受体人群，但显着不太可能发展冠状动脉vasculopathy（p = 0.0361）。G纯合子的平均诊断时间为1240.5天，而C等位基因携带者为2266.5天（p = 0.002）。移植前和移植后1年的临床变量在两组之间是等同的。多因素分析确定GG基因型（p = 0.042，风险比3.01，[95% CI，1.056-10.99]），供体年龄（p = 0.002，风险比1.063，[95% CI，1.029-1.097]），以及第一年3级或以上急性排斥反应事件的数量（p = 0.029，危险比1.11，[95%CI，1.05-1.26]）作为血管病变的显著预测因子。结论：本研究表明，高产量TGF-β 1基因型和心脏移植冠状动脉血管病变的早期发病之间存在相关性。这为心脏移植血管病变的病理生理学提供了重要的见解，并提出了新的治疗方案。
Background: Expression of transforming growth factor-beta 1 (TGF-beta 1) is central to vascular repair due to its effects on smooth muscle cell, monocyte/macrophage, leucocyte, and extracellular matrix accumulation and proliferation. Genetic polymorphism at position +915 of the TGF-beta 1 gene determines the degree of cytokine production in response to injury. We investigated this allelic variation on the development of cardiac transplant-related coronary vasculopathy (CV).Methods: Using sequence-specific primers to the TGF-beta 1 gene region of interest, a polymerase chain reaction (PCR) and gel electrophoresis identified the genotype in 129 cardiac transplant recipients. An association was sought between the presence of a high- (GG) or low/intermediate-producing (CC/GC) genotype and the development of coronary vasculopathy diagnosed by coronary angiography.Results: C allele carriers made up 10.9% of the recipient population but were significantly less likely to develop coronary vasculopathy (p = 0.0361). Mean time to diagnosis was 1240.5 days in G homozygotes relative to 2266.5 days in C allele carriers (p = 0.002). Pre- and 1-year posttransplant clinical variables were equivalent between the 2 groups. Multivariate analysis identified the GG genotype (p = 0.042, hazard ratio 3.01, [95% CI, 1.056-10.99]), donor age (p = 0.002 hazard ratio 1.063, [95% CI, 1.029-1.097]), and number of acute-rejection episodes of grade 3 or greater in the first year (p = 0.029, hazard ratio 1.11, [95% CI, 1.05-1.26]) as significant predictors of vasculopathy.Conclusions: This study demonstrates a correlation between a high-producing TGF-beta 1 genotype and an earlier onset of cardiac-transplant coronary vasculopathy. This gives an important insight into the pathophysiology of cardiac transplant vasculopathy and suggests new treatment options.