Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension
Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension
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DOI：
10.1161/circulationaha.105.601930
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发表时间：
2006-05-30
期刊：
影响因子：
37.8
通讯作者：
Ward, Kenneth
中科院分区：
文献类型：
--
作者：
Elliott, C. Gregory;Glissmeyer, Eric W.;Ward, Kenneth
背景 - 血管反应性测试对于评估肺动脉高压 (PAH) 至关重要。转化生长因子-β II 型受体基因 BMPR2 的突变易导致肺动脉高压的发生，并可能改变对血管扩张剂的反应。先前的研究尚未检查 BMPR2 突变与血管反应性的关系。方法和结果 - 我们确定了 133 名连续的无关的特发性或家族性 PAH 患者。 66 名患者被排除，因为我们缺乏 DNA 样本 (n = 18) 或血管反应性测试的完整数据 (n = 48)。其余67名患者进行了BMPR2 DNA序列变异筛查，并通过基因测序确认了具体变异。将具有非同义 BMPR2 变异的患者的血管反应性与不具有非同义 BMPR2 变异的患者的血管反应性进行比较。我们在 67 名特发性（52 名中的 16 名）或家族性（15 名中的 11 名）PAH 患者中，有 27 名发现了非同义 BMPR2 变异。在 27 名具有非同义 BMPR2 变异的患者中，有 3.7% 的患者出现了血管反应性，在 40 名没有非同义 BMPR2 变异的患者中，有 35% 的患者出现了血管反应性 (P = 0.003)。 27 种非同义变异中有 5 种常见于健康个体。其余 22 名具有 BMPR2 变异的患者均未表现出血管反应性，并且当我们假设所有 15 名家族性 PAH 患者中都存在非同义 BMPR2 变异时，分析保持不变。结论 - 患有家族性或特发性 PAH 和非同义 BMPR2 变异的患者不太可能表现出血管反应性。需要进一步的试验来确定是否可以通过检测 BMPR2 变异来指导长期治疗。
Background - Vasoreactivity tests are fundamental in evaluating pulmonary arterial hypertension (PAH). Mutations of the transforming growth factor-beta type II receptor gene, BMPR2, predispose to the development of pulmonary hypertension and may alter the response to vasodilators. Previous investigations have not examined the relationship of BMPR2 mutations to vasoreactivity.Methods and Results - We identified 133 consecutive unrelated patients with either idiopathic or familial PAH. Sixty-six patients were excluded because we lacked either DNA samples (n = 18) or complete data from a vasoreactivity test (n = 48). The remaining 67 patients were screened for BMPR2 DNA sequence variations, and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymous BMPR2 variations was compared with that of patients without nonsynonymous BMPR2 variations. We found nonsynonymous BMPR2 variations in 27 of 67 patients with idiopathic (n = 16 of 52) or familial (n = 11 of 15) PAH. Vasoreactivity was identified in 3.7% of 27 patients with nonsynonymous BMPR2 variations and in 35% of 40 patients without nonsynonymous BMPR2 variations (P = 0.003). Five of the 27 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 22 patients with BMPR2 variations demonstrated vasoreactivity, and the analysis remained unchanged when we assumed that nonsynonymous BMPR2 variations were present in all 15 patients with familial PAH.Conclusions - Patients with familial or idiopathic PAH and nonsynonymous BMPR2 variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether long-term therapy can be directed by tests for BMPR2 variations.