Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.
Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.
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DOI：
10.1177/2045894018773049
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发表时间：
2018-04
影响因子：
2.6
通讯作者：
Machado RF
中科院分区：
文献类型：
--
作者：
Duarte JD;Kansal M;Desai AA;Riden K;Arwood MJ;Yacob AA;Stamos TD;Cavallari LH;Zamanian RT;Shah SJ;Machado RF
左心衰（HF-PH）背景下肺动脉高压（包括毛细血管前和毛细血管后肺动脉高压（Cpc-PH））发展背后的生物学机制仍不清楚。本研究旨在利用一氧化氮合酶（NOS）基因的候选多态性来探讨NOS在HF-PH中的作用。对118例HF-PH患者的DNA样本进行NOS 3 rs 1799983和NOS 2 rs3730017多态性的基因分型。使用多元回归模型比较基因型组之间的血流动力学测量值。rs 1799983位点T/T基因型患者的跨肺压差（TPG）较其他基因型患者增加近10 mmHg（P = 0.006）。这一发现在94例HF-PH患者的独立队列中得到了重复（P = 0.005）。然而，当在162名毛细血管前肺动脉高压患者中进行测试时，没有观察到相关性。在两个HF-PH队列的联合分析中，平均肺动脉压（mPAP）、舒张期肺动脉压差（DPG）和CpcPH状态也与rs 1799983基因型相关（分别为P = 0.005、P = 0.03和P = 0.02）。在HF-PH患者中，NOS 3 rs 1799983多态性与TPG相关，也可能与mPAP和DPG相关。这些结果表明，内皮NOS（编码的NOS 3）可能参与了观察到的Cpc-PH肺血管重塑，值得进一步研究。
The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.
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