Development of strategy to clarify pathophysiology of rare autoimmune diseases and lead to novel treatment through genetic studies

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H06251
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Collagenous pathology/Allergology
• Research Institution: Institute of Physical and Chemical Research (2017); Kyoto University (2016)
• Principal Investigator: TERAO CHIKASHI 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (60610459)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 高安動脈炎 / 強皮症 / 再発性多発軟骨炎 / 希少疾患 / 遺伝子解析

Outline of Final Research Achievements

We conducted a genome-wide association study (GWAS) followed by a replication study, using a total of 633 Takayasu arteritis cases and 5928 controls. We identified four novel significant loci, namely, PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, and two additional loci which are novel in non-European GWAS, HSPA6/FCGR3A and chr21q.22. Enhancer enrichment analysis suggested NK cell involvement.
We performed trans-ethnic meta-analysis of systemic sclerosis (SSc) GWAS in the Japanese and European populations comprising a total of 4,436 cases and 14,751 controls. We identified GSDMA and PRDM1, both of which are also associated with other autoimmune diseases, as novel susceptibility genes to SSc (p=1.4x10-10 and 6.6x10-10, respectively).
A total of 102 patients with relapsing polychondritis (RP) and 1,000 healthy subjects were genotyped for six HLA classical loci. We identified a total of three novel susceptibility HLA alleles, namely, HLA-DRB1*16:02, HLA-DQB1*05:02, and HLA-B*67:01.

Free Research Field

臨床遺伝学