Functional analysis of RXRB genetically identified as a susceptibility gene for systemic sclerosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokai University
• Principal Investigator: Oka Akira 東海大学, 医学部, 講師 (80384866)
• Co-Investigator(Kenkyū-buntansha): 浅野 善英 東京大学, 医学部附属病院, 准教授 (60313029)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 全身性強皮症 / 遺伝子

Outline of Final Research Achievements

We have already identified a susceptibility mutation on the RXRB gene (retinoic acid receptor) that carries a strong genetic risk for systemic sclerosis (SSc). Therefore, they investigated the function of the mutation using fibroblasts isolated from patient-affected areas. Our studies showed that in the presence of retinoic acid, the expression of a gene group involved in the cell cycle was significantly increased only in cells with the mutation. This group containds cyclin-dependent kinase 1 (CDK1), and molecules targeting CDK1 have already shown promise as a treatment for SSc, it is strongly suggested that this mutation may be biologically involved in the pathogenesis of SSc.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

全身性強皮症の遺伝学的なリスクと生物学的な機能を示した世界初の研究成果となる。すなわち、リスクの遺伝子型がすでに明らかになっている遺伝子とSScとの生物学的機能の関連を明らかにすることは、遺伝子型情報をベースとする、全く新しい診断、予防ならびに治療技術開発の可能性を秘めている。