The analsyis of genetic structural abnormality in patient with plumonary hypertension in comparison with centenerian and risk assesesment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17162
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Keio University
• Principal Investigator: Suzuki Hisato 慶應義塾大学, 医学部(信濃町), 講師 (80783042)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺高血圧症 / 全ゲノム解析 / 遺伝子構造異常 / 血管内皮細胞

Outline of Final Research Achievements

Whole genome sequencing was performed on pulmonary hypertension patients with unknown genetic background to explore the pathogenesis of the disease.We assumed a monogenetic disease and a polygenetic disease for pulmonary hypertension. For the monogenetic disease, we attempted to detect abnormalities in gene structure, which are difficult to detect by GWAS and exome sequencing. Whole genome sequencing was performed on patients from 11 families, and no gene structural abnormalities were detected. FOr polygenic disease approach, we focused on rare variants that can cause abnormalities in vascular tone, vascular wall elasticity, lipid metabolism, and coagulation, and examined their interactions. Three rare variants were detected in patients from 11 families, but their pathological significance could not be established.

Free Research Field

遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究では肺高血圧症患者に対する全ゲノムシーケンスを実施し、これまで多く実施されてきたGWASやエクソームシーケンスでは検出困難な遺伝子構造異常、コピー数多型を検出し、それらを臨床医が評価しやすいパイプラインを構築することができた。この成果は肺高血圧症のみならず他の疾患でも役立てることが可能である。
本研究を通じて、肺高血圧症の原因として３つの遺伝子の関与を検出し、それぞれの意義について検討したが、疾患との関連性の確立には至らなかった。今後、機能解析を通じてその病的意義を確立することで疾患の病態解明に役立つと考えられる。