Research on genetic factors of atopic dermatitis and psoriasis

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09793
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nippon Medical School
• Principal Investigator: SAEKI Hidehisa 日本医科大学, 大学院医学研究科, 大学院教授 (80235093)
• Co-Investigator(Kenkyū-buntansha): 玉利 真由美 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, チームリーダー (00217184) ; 廣田 朝光 東京慈恵会医科大学, 医学部, 講師 (50435674)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: アトピー性皮膚炎 / 乾癬 / 遺伝要因

Outline of Final Research Achievements

We conducted an initial genome-wide association study (GWAS) and a replication study of psoriasis vulgaris (PsV) in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms (SNPs) with PsV risk at TNIP1 and the MHC region. By updating the HLA imputation reference panel of Japanese (n = 908), we demonstrated that HLA-A*02:07 was the most significant association with PsV. Our PsV GWAS in Japanese highlighted novel genetic architecture of PsV.
Sixty-five Japanese patients with psoriasis underwent anti-TNF-alpha treatment. We genotyped SNPs in TNFA, TNFRSF1B and TNFAIP3 genes which had been shown to be associated the response to anti-TNF-alpha treatment in Western countries. There was no significant association of these three SNPs with response to anti-TNF-alpha treatment in Japan. The difference between the two studies lies in the TNF-alpha inhibitors used.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎や乾癬の遺伝要因の解析で、亜型や治療反応性に注目した解析は極めて少なく、本研究の特色と言える。遺伝要因に関しては人種差があるため、欧米で行われた解析も日本人の集団で確認する必要がある。亜型や治療反応性で解析することにより、症例ごとにより適切な治療を選択することができるようになる点に本研究の意義がある。分子標的薬を用いた新しい治療の有効性は高いが費用も高いため、予め効果が期待できる患者を選別できれば、無駄な医療費を掛けずに済み、医療経済上の効果も大きい。