Exploration of the genes which are responsible for the pathogenesis of Takayasu arteritis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670399
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ISOBE MITSUAKI 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80176263)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 高安動脈炎 / 一塩基多型 / インフラマソーム

Outline of Final Research Achievements

Takayasu arteritis (TA) is an autoimmune systemic arteritis of unknown etiology. We have identified that single nucleotide polymorphisms (SNPs) of MLX gene, which encodes MLX transcription factor, was significantly associated with clinical manifestations of TA by genome-wide association study. The SNPs of MLX (rs665268) is a missense mutation of MLX that alters the Gln139 to Arg(Q139R). As Gln139 is located on the DNA binding site of MLX, we hypothesized that the mutation of Q139R on MLX, which alters the electric charge of the amino acid may enhance the formation of the MLX-DNA complex. Then, based on our experimental results, we concluded that MLX-Q139R mutation plays a crucial role in the pathogenesis of TA through facilitating inflammasome formation, which in turn promoting proliferation and adhesion ability of aorta-resident cells, a pathological manifestation seen in the aortas of TA.

Free Research Field

循環器内科学