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2020 Fiscal Year Final Research Report

Exploring novel genetic factors associated with intravenous immunoglobulin therapy-unresponsiveness in Kawasaki disease patients

Research Project

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Project/Area Number 18K15666
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionShinshu University

Principal Investigator

Amano Yuji  信州大学, 学術研究院医学系, 助教 (50624681)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywords川崎病 / IVIG療法抵抗性 / 遺伝子解析 / pooled genome sequencing
Outline of Final Research Achievements

We performed exome sequencing followed by deep sequencing using pooled genomic DNA derived from 30 of IVIG-unresponsive Kawasaki disease (KD) patients. As a result, we selected 8 variants as candidates. Individual genotyping showed that a low frequency missense variant located in SMURF2 locus is concentrated in IVIG-unresponsive KD patients(p=4.5e-5). We examined clinical characteristics of KD patients harboring this variant, and found that this variant is a protective factor for the development of coronary artery lesions in IVIG-unresponsive KD patients(p=0.0365).

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

SMURF2は、IVIG抗炎症作用および川崎病急性期炎症と密接に関与するTGF-betaシグナルのネガティブレギュレーターとして知られている。アミノ酸置換を伴う本バリアントは、SMURF2の分子機能に影響を及ぼす可能性が高い。その詳細解析はIVIGの抗炎症効果の分子機序解明につながる可能性を秘めている。更に本バリアントは日本人の約0.6%がヘテロに保有する低頻度バリアントであるにもかかわらず、約13%のIVIG不応性川崎病患者がヘテロに保有していた(OR(95%CI)=25.9(8.3-80.6))。更なる検証を行うことにより、IVIG不応性予測指標へと繋がる事が期待される。

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Published: 2022-01-27  

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