{
  "abstract": "Objectives Eosinophilic granulomatosis with polyangiitis (EGPA) is classified as a subtype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A recent genome-wide association study (GWAS) of EGPA in populations of European ancestry reported several susceptibility loci. In view of population differences in genetic factors of AAV, we made an attempt to examine the contribution of these loci to EGPA in a Japanese population.Methods The EGPA-associated variants in LPP, TSLP, IRF1/IL5, HLA, CDK6, 10p14 and 12q21 in European populations (EUR) were analysed in a total of 103 Japanese patients with EGPA, including 48 myeloperoxidase (MPO)-ANCA-positive and 45 ANCA-negative patients. Allele frequency data on approximately 60 000 Japanese individuals from the Japanese Multi Omics Reference Panel served as the controls.Results An increasing tendency in TSLP rs1837253 C allele was observed in total EGPA, MPO-ANCA-positive EGPA and ANCA-negative EGPA. In addition, association of HLA-DRB1*07:01 was observed in total EGPA and MPO-ANCA-positive EGPA. These findings supported the previous findings in the EUR. On the other hand, unlike in the EUR, association of DRB1*09:01 was observed in Japanese EGPA. With respect to amino acid residues in HLA-DRβ1, Val 78 encoded by DRB1*07:01 and *09:01 was associated with total EGPA and MPO-ANCA-positive EGPA with genome-wide significance (p<5.0E−08). Association with the other loci was not observed in Japanese EGPA.Conclusion TSLP was suggested to be associated with EGPA both in the European and Japanese populations regardless of the ANCA status. In HLA-DRB1, both shared and population-specific susceptibility alleles were observed.",
  "authors": [
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan"
      ],
      "name": "Aya Kawasaki"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan",
        "H.U. Group Research Institute G.K, Tokyo, Japan"
      ],
      "name": "Ikue Ito-Naito"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan"
      ],
      "name": "Mina Sato"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan"
      ],
      "name": "Yuka Kawamura"
    },
    {
      "affiliations": [
        "Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Okayama, Japan",
        "Department of Clinical Epidemiology, Kochi University, Kochi, Japan"
      ],
      "name": "Ken-ei Sada"
    },
    {
      "affiliations": [
        "Division of Hematology and Rheumatology, National Defense Medical College, Tokorozawa, Japan"
      ],
      "name": "Kenji Itoh"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan"
      ],
      "name": "Nobuyuki Ono"
    },
    {
      "affiliations": [
        "Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan"
      ],
      "name": "Fumio Hirano"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University, Tokyo, Japan"
      ],
      "name": "Tomoaki Higuchi"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Juntendo University Koshigaya Hospital, Koshigaya, Japan"
      ],
      "name": "Shigeto Kobayashi"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Ome Medical Center, Ome, Japan"
      ],
      "name": "Kenji Nagasaka"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Institute of Science Tokyo, Tokyo, Japan"
      ],
      "name": "Takahiko Sugihara"
    },
    {
      "affiliations": [
        "Department of General Medicine, Nara Medical University, Nara, Japan"
      ],
      "name": "Takashi Fujimoto"
    },
    {
      "affiliations": [
        "Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, Tokyo, Japan"
      ],
      "name": "Makio Kusaoi"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Yuya Kondo"
    },
    {
      "affiliations": [
        "Division of Immunology and Rheumatology, Department of Internal Medicine 3, Hamamatsu University School of Medicine, Hamamatsu, Japan"
      ],
      "name": "Kumiko Shimoyama"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan",
        "Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"
      ],
      "name": "Keita Yamashita"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan",
        "Department of Nephrology, Ushiku Aiwa General Hospital, Ushiku, Japan"
      ],
      "name": "Takashi Higuchi"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan"
      ],
      "name": "Hajime Kono"
    },
    {
      "affiliations": [
        "Division of Immunology and Rheumatology, Department of Internal Medicine 3, Hamamatsu University School of Medicine, Hamamatsu, Japan"
      ],
      "name": "Noriyoshi Ogawa"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Isao Matsumoto"
    },
    {
      "affiliations": [
        "Department of Nephrology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Kunihiro Yamagata"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Takayuki Sumida"
    },
    {
      "affiliations": [
        "School of Medicine, Juntendo University, Tokyo, Japan"
      ],
      "name": "Hiroshi Hashimoto"
    },
    {
      "affiliations": [
        "Okayama University, Okayama, Japan"
      ],
      "name": "Hirofumi Makino"
    },
    {
      "affiliations": [
        "Department of Nephrology and Rheumatology, Kyorin University, Tokyo, Japan",
        "Department of Internal Medicine, Kichijoji Asahi Hospital, Tokyo, Japan"
      ],
      "name": "Yoshihiro Arimura"
    },
    {
      "affiliations": [
        "Department of Rheumatology, International University of Health and Welfare School of Medicine, Chiba, Japan"
      ],
      "name": "Masayoshi Harigai"
    },
    {
      "affiliations": [
        "Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, Tokyo, Japan"
      ],
      "name": "Naoto Tamura"
    },
    {
      "affiliations": [
        "Molecular and Genetic Epidemiology Laboratory, University of Tsukuba Institute of Medicine, Tsukuba, Japan"
      ],
      "name": "Naoyuki Tsuchiya"
    }
  ],
  "title": "Genetic associations of eosinophilic granulomatosis with polyangiitis in the Japanese population: exploring similarities and differences with European populations",
  "uid": "42d5bda8-2034-53b5-b0a1-73b5c8f0a688"
}