Kobayashi Hiroshi, Nakata Norio, Izuka Sayoko, Hongo Kenichi, Nishikawa Masako
Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
Department of Pediatrics, The Jikei University of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
Mol Genet Metab Rep. 2024 Oct 13;41:101152. doi: 10.1016/j.ymgmr.2024.101152. eCollection 2024 Dec.
Fabry disease is the most frequently occurring form of lysosomal disease in Japan, and is characterized by a wide variety of conditions. Primarily, the three major types of concerns associated with Fabry disease observed during adulthood that must be prevented are central nervous system, renal, and cardiac complications. Cardiac complications, such as cardiomyopathy, cardiac muscle fibrosis, and severe arrhythmia, are the most common mortality causes in patients with Fabry disease. To predict cardiac complications of Fabry disease, we extracted RNA from the venous blood of patients for cap analysis of gene expression (CAGE), performed likelihood ratio tests for each RNA expression dataset obtained from individuals with and without cardiac complications, and analyzed the correlation between cardiac functional factors observed using magnetic resonance imaging data extracted using artificial intelligence algorithms and RNA expression. Our findings showed that CHN1 expression was significantly higher in male Fabry disease patients with cardiac complications and that it could be associated with many cardiac functional factors. encodes a GTPase-activating protein, chimerin 1, which is specific to the GTP-binding protein Rac (involved in oxidative stress generation and the promotion of myocardial fibrosis). Thus, CHN1 is a potential predictive biomarker of cardiac complications in Fabry disease; however, further studies are required to confirm this observation.
法布里病是日本最常见的溶酶体病类型，具有多种临床表现。主要而言，成年期法布里病患者必须预防的三大主要问题是中枢神经系统、肾脏和心脏并发症。心脏并发症，如心肌病、心肌纤维化和严重心律失常，是法布里病患者最常见的死亡原因。为了预测法布里病的心脏并发症，我们从患者静脉血中提取RNA进行基因表达帽分析（CAGE），对有和没有心脏并发症的个体获得的每个RNA表达数据集进行似然比检验，并分析使用人工智能算法提取的磁共振成像数据观察到的心脏功能因素与RNA表达之间的相关性。我们的研究结果表明，CHN1在患有心脏并发症的男性法布里病患者中表达显著更高，并且它可能与许多心脏功能因素相关。CHN1编码一种GTP酶激活蛋白——嵌合蛋白1，它是GTP结合蛋白Rac特有的（参与氧化应激的产生和心肌纤维化的促进）。因此，CHN1是法布里病心脏并发症的潜在预测生物标志物；然而，需要进一步研究来证实这一观察结果。
