BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives
BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives
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DOI：
10.1183/09031936.02.01762002
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发表时间：
2002-09-01
影响因子：
24.3
通讯作者：
Morse, JH
中科院分区：
文献类型：
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作者：
Humbert, M;Deng, Z;Morse, JH
本研究调查了接触食欲抑制剂芬氟拉明和右芬氟拉明后出现肺动脉高压（PAH）的患者是否存在骨形态发生蛋白受体2（BMPR 2）基因突变，正如原发性肺动脉高压中所报告的那样。对33名不相关的散发性肺动脉高压患者和两名患有肺动脉高压的姐妹篇进行了BMPR 2突变检查，她们都服用了芬氟拉明衍生物，以及130名正常对照。PAH患者也进行了心脏导管插入术和体重测定。在33名无关患者中的3名（9%）中发现了3个BMPR 2突变，预测BMPR-II蛋白一级结构的变化，在两姐妹篇中发现了第四个突变。在130名正常对照中未发现BMPR 2突变。这种频率差异具有统计学意义。此外，突变阳性患者在患病前的芬氟拉明暴露时间略短于突变阴性患者，当两姐妹篇被纳入分析时，差异具有统计学意义。本发明的作者已经检测到骨形态发生蛋白受体2突变，该突变在一般人群中似乎是罕见的，但可能与芬氟拉明衍生物的暴露联合收割机结合，患上严重肺动脉高压的风险。
This study investigated whether patients developing pulmonary arterial hypertension (PAH) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene, as reported in primary pulmonary hypertension.BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom bad taken fenfluramine derivatives, as well as in 130 normal controls. The PAH patients also underwent cardiac catheterisation and body mass determinations.Three BMPR2 mutations predicting changes in the primary structure of the BMPR-II protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No BMPR2 mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients a difference that was statistically significant when the two sisters were included in the analysis.In conclusion, the present authors have detected bone morphogenetic protein receptor 2 mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe pulmonary arterial hypertension.