Yilmaz E, Mir S, Berdeli A
Department of Pediatric Nephrology, Ege University, Izmir, Bornova, Turkey.
Transplant Proc. 2009 Dec;41(10):4361-5. doi: 10.1016/j.transproceed.2009.09.080.
Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO.
慢性移植肾肾病（CAN）是一种由潜在肾脏疾病叠加环境和遗传因素引起的复杂现象。CAN的发展始于进行性肾微血管损伤。内皮细胞在血管张力、通透性和重塑的调节中起关键作用。由于内皮型一氧化氮合酶（eNOS）功能的基因变异导致基础一氧化氮（NO）释放减少，可能易患高血压、血栓形成、血管痉挛和动脉粥样硬化，所有这些都促成了CAN的发展。我们分析了81例肾移植儿童中eNOS基因第7外显子的G894T突变与CAN的关系。20例发生CAN的患者接受了肾活检以进行组织学确诊。在CAN中观察到蛋白尿和高血压。我们选择了173名健康对照者。通过聚合酶链反应-限制性片段长度多态性分析确定eNOS基因的G894T多态性。该组包括33名男性和48名女性受试者，他们接受了32例亲属活体移植和49例尸体供体（DD）移植。供体年龄（岁）为32.7±13.7，尸体供体病例的HLA A、B、DR错配数为3.5±0.79。基因型分布分别为ENOS GG/GT/TT 48%、33%、19%。G等位基因频率为64.8%；T等位基因频率为35.2%。ENOS G894T基因多态性似乎不影响肾移植的长期结果。受者的ENOS G894T基因多态性并未改变慢性移植肾失功的风险。即使这种多态性会影响NO的合成和生物活性，但许多血管活性因子可能会抑制NO的有益作用。
