Creation of precision medicine for aortic disease by comprehensive gene analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Kansai Medical University
• Principal Investigator: OKADA Takayuki 関西医科大学, 医学部, 准教授 (60421278)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: Genome Omics / Genetic Variant / Precision Medicine / Cardiovascular Diseases / Biomarker

Outline of Final Research Achievements

The FBN1 gene is highly polymorphic, leading to many variants of uncertain significance (VUS). Our study on patients with aortic diseases linked to FBN1 mutations revealed that many lacked typical characteristics like tall stature and skeletal deformities, indicating possible ethnic differences. Through our expression and functional analyses, we found instances with no mutations, Marfan-related disorders with FBN2 mutations, and ocular and neurological cases with FBN1 variants, highlighting the diverse manifestations of these mutations.
Aortic diseases are often fatal and a leading cause of sudden death. Their onset mechanisms and timing are largely unknown, complicating emergency interventions. Genetic predispositions have been suggested, and our findings on FBN1 variants show that advancing VUS analysis can improve understanding of environmental interactions, aiding in the development of preventive and precision medicine.

Free Research Field

Cardiovascular disease

Academic Significance and Societal Importance of the Research Achievements

自験例のMS症候群及び類縁疾患遺伝子パネルシークエンス検査を利用し、25%にFBN1遺伝子バリアントを同定し得た。心臓大動脈疾患が顕性遺伝の家族集積を示す場合はもちろん、たとえ家族歴や教科書的な特徴的身体所見がなくても、若年発症例(50歳未満発症)であればFBN1遺伝子を中心にした心大動脈形態を支持する弾性線維構造やシグナル異常が関与しうる可能性が示唆された。心大動脈疾患のVUSバリアントの病原性を再検討すると同時に、包括的なゲノム・オミックス情報の蓄積がプレシジョンメディシンの発展に重要な役割を果たすと考える。