Detection of susceptibility genes associated with autoimmune rheumatic diseases in the Japanese population and its translation into genome medicine.

本研究旨在寻找与日本人群自身免疫性风湿病易感性、临床特征和药物不良反应相关的基因多态性。TLR7与系统性红斑狼疮(SLE)和SPP1与类风湿关节炎(RA)的相关性是通过国际多中心合作确定的。通过与国家风湿病中心的合作，检测到IRF2、PHRF1-IRF7与SLE、UBE2L3与系统性硬化症、IRF5与髓过氧化物酶-抗中性粒细胞胞浆抗体相关小血管炎的相关性。此外，人类白细胞抗原-DRB1*13：02和DRB1*14：03对系统性红斑狼疮有保护作用。在药物不良反应方面，发现人类白细胞抗原-A*31：01与类风湿关节炎甲氨蝶呤相关性间质性肺疾病有关。这些结果将为日本建立针对自身免疫性风湿病的基因组医学提供有价值的信息。

This study aimed at finding polymorphisms associated with susceptibility to autoimmune rheumatic diseases, as well as with clinical characteristics and adverse reaction to drugs, in the Japanese population. Association of TLR7 with systemic lupus erythematosus (SLE) and SPP1 with rheumatoid arthritis (RA) was identified through international multicenter collaboration. Association of IRF2, PHRF1-IRF7 with SLE, UBE2L3 with systemic sclerosis, and IRF5 with myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis was detected through collaboration with national rheumatology centers. In addition, HLA-DRB1*13:02 and DRB1*14:03 were found to be protective against SLE. With respect to adverse reactions to drugs, HLA-A*31:01 was found to be associated with methotrexate associated interstitial lung disease in RA. These results will provide valuable information for the establishment of genome medicine for autoimmune rheumatic diseases in Japan.