九州大学大学院医学研究院循環器内科学・共同研究員円山 信之Nobuyuki EnzanDepartment of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu UniversityAbstractDilated cardiomyopathy (DCM) is the third most common cause of heart failure and the most common etiology for heart transplantation. Recently novel drugs, such as angiotensin receptor/neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors, became available for heart failure. However, there is no specific treatment for each etiology, including DCM. To develop personalized medicine for cardiomyopathy, we proposed the proteomic analysis for DCM utilizing nation-wide registry. First, we developed nationwide registry JROADHF-NEXT and collected > 4,000 individuals with > 3,000 blood and urine samples. Median follow-up period in JROADHF-NEXT was 2.0 years. Among them, we measured 92 proteins for 150 DCM samples. We tested association between all 92 proteins with cardiovascular death/heart failure rehospitalization. As a result, BNP, RAGE, REN and FGF-23 were statistically significant (false discovery rate < 0.05). These proteins can be biomarkers to predict worse outcomes in DCM patients. はじめに心不全は主たる死因の 1 つであるが，多様な症候群であり，他分野と比較して治療開発が遅れている．我々は近年日本人 20 万人を超える心不全ゲノムワイド関連解析を行い，HFrEF (heart failure with reduced ejection fraction) は HFpEF (heart failure with preserved ejection fraction) と比較し，より均一な疾患群であり，多くの遺伝子シグナルが同定出来ることを報告した 1）．このことは蛋白質プロファイルについても同様に HFrEF では特異的なシグナルが見つかる可能性を示唆している．拡張型心筋症は心不全の主たる原因であり，心不全入院や突然死を引き起こすため，正確な診断・予後予測・正確な治療介入が不可欠である．このためには心筋症で特異的に生じているシグナルや新規バイオマーカーの同定が必要である．しかし生体内では多くの蛋白質が複雑に作用しており，これらの― 133 ―心筋症に対する網羅的蛋白質解析による個別化医療の確立Development of personalized medicine for cardiomyopathy by proteomics
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