中国肺动脉高压患者携带 BMPR2 或 EIF2KAK4 变异体的临床特征和生存情况。
Clinical characteristics and survival of Chinese patients diagnosed with pulmonary arterial hypertension who carry BMPR2 or EIF2KAK4 variants.
机构信息
State Key Laboratory of Cardiovascular Disease, Center of Pulmonary Vascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, North Lishi Road, Xicheng District, No.167, Beijing, China.
State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Disease, Diagnostic Laboratory Service, Fuwai Hosptial, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, North Lishi Road, Xicheng District No.167, Beijing, China.
出版信息
BMC Pulm Med. 2020 May 29;20(1):150. doi: 10.1186/s12890-020-01179-7.
BACKGROUND
Variants in the gene encoding bone morphogenetic protein receptor type II (BMPR2) are the most common genetic cause of pulmonary arterial hypertension (PAH), whereas biallelic variants in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH). Racial background may influence the clinical characteristics of patients diagnosed with PAH or PVOD/PCH. Here, we compared the clinical characteristics and survival between patients with BMPR2 variants or EIF2AK4 variants in a Chinese population.
METHODS
Heterozygous variants in BMPR2 and homozygous or compound heterozygous biallelic EIF2AK4 variants predicted to be deleterious were identified as potentially causal. Clinical and radiological data were collected and analysed. The primary outcomes were death or lung transplantation. Hazard ratios (HRs) for death or transplantation associated with the presence of BMPR2 or biallelic EIF2AK4 variants were calculated using Cox proportional hazards models to analyse patient survival.
RESULTS
Two hundred thirty-two patients with PAH were enrolled for genetic testing, and PAH patients with associated conditions were excluded from the study. Forty-five patients with BMPR2 variants and 11 patients with biallelic EIF2AK4 variants were recruited. PAH patients with BMPR2 or biallelic EIF2AK4 variants presented symptoms at the ages of 25.57 ± 10.17 years and 31.6 ± 9.38 years, respectively. The whole group of patients showed female dominance either with BMPR2 variants or biallelic EIF2AK4 variants. Specific radiological abnormalities are more prominent in EIF2AK4 variant carriers but can also be found in some patients with BMPR2 variants. Biallelic EIF2AK4 variant carriers had worse survival than BMPR2 variant carriers (p < 0.0001).
CONCLUSIONS
Clinical pictures of PAH patients with BMPR2 and biallelic EIF2AK4 variants in the Chinese population differ from other populations by a younger age at diagnosis and demonstrate female dominance in the whole patient group. High-resolution chest CT can help assist in differentiating PAH with PVOD/PCH. BMPR2 variants and biallelic EIF2AK4 variants are associated with adverse outcomes, but the survival of patients with biallelic EIF2AK4 variants is dismal.
背景
骨形成蛋白受体 2 型（BMPR2）基因变异是肺动脉高压（PAH）最常见的遗传原因，而真核翻译起始因子 2α激酶 4 基因（EIF2AK4）的双等位基因变异则与肺静脉闭塞病/肺毛细血管血管瘤病（PVOD/PCH）有关。种族背景可能会影响诊断为 PAH 或 PVOD/PCH 的患者的临床特征。在这里，我们比较了中国人群中 BMPR2 变异或 EIF2AK4 变异患者的临床特征和生存情况。
方法
鉴定出 BMPR2 杂合变异和预测为有害的 EIF2AK4 双等位基因纯合或复合杂合变异作为潜在的致病原因。收集和分析临床和影像学数据。主要结局是死亡或肺移植。使用 Cox 比例风险模型计算与 BMPR2 或双等位基因 EIF2AK4 变异相关的死亡或移植的风险比（HRs），以分析患者的生存情况。
结果
对 232 名 PAH 患者进行了基因检测，排除了伴有相关疾病的 PAH 患者。共招募了 45 名 BMPR2 变异患者和 11 名双等位基因 EIF2AK4 变异患者。BMPR2 或双等位基因 EIF2AK4 变异患者的 PAH 患者的症状出现在 25.57±10.17 岁和 31.6±9.38 岁。整个患者群体无论是否存在 BMPR2 变异或双等位基因 EIF2AK4 变异，均以女性为主。EIF2AK4 变异携带者的特定影像学异常更为突出，但也可在一些 BMPR2 变异患者中发现。双等位基因 EIF2AK4 变异携带者的生存情况比 BMPR2 变异携带者差（p<0.0001）。
结论
中国人群中 BMPR2 和双等位基因 EIF2AK4 变异的 PAH 患者的临床表现与其他人群不同，表现为诊断时年龄较小，且整个患者群体以女性为主。高分辨率胸部 CT 有助于区分 PAH 与 PVOD/PCH。BMPR2 变异和双等位基因 EIF2AK4 变异与不良结局相关，但双等位基因 EIF2AK4 变异患者的生存情况较差。
Zotero 插件