Novel variants in chronic theromboembolic pulmonary hypertension

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15982
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Tohoku University
• Principal Investigator: Yaoita Nobuhiro 東北大学, 医学系研究科, 非常勤講師 (00735368)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 慢性血栓塞栓性肺高血圧症 / 急性肺塞栓症 / 一塩基変異多型

Outline of Final Research Achievements

Chronic thromboembolic pulmonary hypertension (CTEPH) is a fatal disease entity of pulmonary hypertension (PH) characterized by obstruction of the major pulmonary arteries by organized thrombus and pulmonary vascular remodeling. The genetic background of CTEPH was not revealed so far. We checked the single nucelotide polimrphisms(SNPs) in CTEPH patients, which was related to idiopathic pulmonary arterial hypertension (IPAH) or acute pulmonary embolism (APE).it was revealed that CTEPH patients did not have any non-synonymous SNPs related to IPAH, but they had non-synonymous SNPs related with APE such as F5, MTHFR and THBD. Moreover, in CTEPH patients who did not have ha history of APE,SNPs of THBD was significantly higher than in healthy subjects. Furthermore, thrombin-activated fibrinolysis inhibitor was activated in CTEPH patients who had the SNPs of THBDs. Taken together, CTEPH patients had SNPs related to APE, even though CTEPH patients did not have history of APE.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

肺動脈内に生じた器質化血栓により生じる慢性血栓塞栓性肺高血圧症(CTEPH)は予後の悪い難病である。急性肺塞栓症(APE)の合併症と考えられるが、APEの既往のないCTEPH患者も多い。このためCTEPHの病態がAPEと似ているのか不明であった。本研究では、世界で初めてCTEPH患者の遺伝的背景を解析し、CTEPH患者にはAPEの危険因子となる遺伝的背景があることがわかった。また、APEの既往のないCTEPH患者もAPEの危険因子となる遺伝的背景があることがわかった。このことからCTEPHとAPEが類似した病態である可能性が示唆された。