Loukanov Tsvetomir, Hoss Katharina, Tonchev Pentcho, Klimpel Homa, Arnold Raul, Sebening Christian, Karck Matthias, Gorenflo Matthias
Department of Cardiac Surgery, Surgical Clinic, University of Heidelberg, Germany.
Cardiol Young. 2011 Apr;21(2):161-9. doi: 10.1017/S1047951110001630. Epub 2010 Dec 10.
Intra-cardiac repair of congenital cardiac diseases in children with left-right shunt is often associated with acute elevation of pulmonary artery pressure following cardiopulmonary bypass. We studied the correlation between the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and pulmonary hypertension in children with congenital cardiac diseases.
A total of 80 children with congenital cardiac diseases at a median age of 3.8 years, ranged 0.1-36.2 years, and 136 controls were enrolled. Most patients presented with significant left-to-right shunt - pulmonary-to-systemic blood flow of 2.8, with a range from 0.6 to 7.5. In all, 40 out of 80 children showed pulmonary hypertension with mean pressure of 42, ranged 26-82, millimetres of mercury. Thirty-one out of 40 children underwent intra-cardiac repair and 15 out of 31 operated patients were found to have an acute elevation of pulmonary artery pressure after cardiopulmonary bypass. The Glu298Asp polymorphism was identified using polymerase chain reaction and restriction fragment length polymorphism. Both in patients and in controls, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The gene frequency for Glu298Glu, Glu298Asp and Asp298Asp was not different in the control group compared to the patients (Armitage trend test: p = 0.37). The endothelial nitric oxide synthase polymorphism was related to acute post-operative elevation of pulmonary artery pressure (genotypic frequency 53.3 versus 25%; Armitage trend test: p = 0.038). In addition, the allelic frequency of the Glu298Asp was related to post-operative pulmonary hypertension (Fischer's exact test: p = 0.048). The positive predictive value was 71.43%.
Patients with left-to-right shunt are more likely to develop acute elevation of pulmonary artery pressure after cardiopulmonary bypass when presenting with the Glu298Asp polymorphism of the gene endothelial nitric oxide synthase. This could be used as a genetic marker for the predisposition for the development of pulmonary hypertension after intra-cardiac repair.
患有左右分流的儿童先天性心脏病进行心内修复时，体外循环后常伴有肺动脉压力急性升高。我们研究了内皮型一氧化氮合酶基因Glu298Asp多态性与先天性心脏病患儿肺动脉高压之间的相关性。
共纳入80例先天性心脏病患儿，中位年龄3.8岁，年龄范围0.1 - 36.2岁，以及136例对照。大多数患者存在明显的左向右分流——肺循环与体循环血流量之比为2.8，范围为0.6至7.5。80例患儿中，40例出现肺动脉高压，平均压力为42毫米汞柱，范围为26 - 82毫米汞柱。40例患儿中有31例接受了心内修复，31例手术患者中有15例在体外循环后出现肺动脉压力急性升高。采用聚合酶链反应和限制性片段长度多态性方法鉴定Glu298Asp多态性。在患者和对照中，基因型分布均符合Hardy-Weinberg平衡。与患者相比，对照组中Glu298Glu、Glu298Asp和Asp298Asp的基因频率无差异（Armitage趋势检验：p = 0.37）。内皮型一氧化氮合酶多态性与术后肺动脉压力急性升高相关（基因型频率53.3%对25%；Armitage趋势检验：p = 0.038）。此外，Glu298Asp的等位基因频率与术后肺动脉高压相关（Fisher精确检验：p = 0.048）。阳性预测值为71.43%。
患有左右分流的患者，当存在内皮型一氧化氮合酶基因Glu298Asp多态性时，体外循环后更易发生肺动脉压力急性升高。这可作为心内修复后肺动脉高压易感性的遗传标志物。
