Functional Analysis of Novel MR Binding Factor Evi1 and Clinical Significance of its SNP in Prediction of Hypertension Onset

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860646
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Rie Jo 慶應義塾大学, 医学部(信濃町), 共同研究員 (30464861)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ミネラルコルチコイド受容体 / 転写共役因子 / GWAS解析 / ヒストンメチル化修飾酵素 / Evi-1

Outline of Final Research Achievements

Mineralocorticoid receptor (MR) is involved in the development of hypertension and its detailed molecular mechanism has been focused. Evi-1 was identified as a candidate for novel MR-interacting protein through LC-MS/MS screening method. Evi-1 has SET domain, which includes histone methylation activity, in the whole molecule “Evi-1c”, but another isoform “Evi-1a”, which lacks SET domain, is supposed to act as dominant negative for Evi-1c. This study elucidated that Evi-1c functions as corepressor of MR but co-expression of Evi-1a suppresses the activity of Evi-1c. The recent GWAS results revealed that a certain SNP of Evi-1 gene is associated with hypertension or chronic kidney disease. It remains to be investigated whether this SNP might determine the ratio of Evi-1c/Evi-1a, leading to the change of MR sensitivity.

Free Research Field

内分泌学