Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever

• Project/Area Number: 26860477
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Shinshu University
• Principal Investigator: KISHIDA Dai 信州大学, 学術研究院医学系(医学部附属病院), 助教 (50467180)
• Research Collaborator: NAKAMURA Akinori 信州大学, 医学部, 特任教授 (10303471) ; YAZAKI Masahide 信州大学, 学術研究院医学系, 准教授 (70372513)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 家族性地中海熱 / 自己炎症疾患 / MEFV遺伝子 / 遺伝型 / 表現型 / コルヒチン / 遺伝子診断 / 月経 / 自己炎症性疾患 / 臨床像 / 民族差

Outline of Final Research Achievements

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. We analyzed patients clinically diagnosed as having FMF to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients.
The most frequent mutation in Japanese patients was E148Q, followed by M694I, L110P, P369S, and R408Q. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not.
Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.

Research Products

• [Journal Article] Fever of unknown origin in the outpatient setting: A retrospective analysis of 30 cases of familial Mediterranean fever (2016)
  • Author(s): Kunimatsu J, Maeda J, Watanabe R, Kato O, Kishida D, Yazaki M, Nakamura A.
  • Journal Title: Japanese Journal of Clinical Immunology Volume: 39 Issue: 2 Pages: 130-139
  • DOI: 10.2177/jsci.39.130
  • NAID: 130005152243
  • ISSN: 0911-4300, 1349-7413
  • Peer Reviewed
• [Journal Article] Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. (2015)
  • Author(s): Yasunami M, Nakamura H, Nakamura A, Yazaki M, Kishida D et al.
  • Journal Title: PLoS One Volume: May 14;10(5) Issue: 5 Pages: e0125938-e0125938
  • DOI: 10.1371/journal.pone.0125938
  • NAID: 120007100158
  • Peer Reviewed / Open Access
• [Journal Article] Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations. (2014)
  • Author(s): Kishida D, Nakamura A, Yazaki M, Tsuchiya-Suzuki A, Matsuda M, Ikeda S.
  • Journal Title: Arthritis Res Ther. Volume: 16 Issue: 5 Pages: 439-439
  • DOI: 10.1186/s13075-014-0439-7
  • Peer Reviewed / Open Access
• [Journal Article] Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients. (2014)
  • Author(s): Migita K, Agematsu K, Yazaki M, Nonaka F, Nakamura A, Toma T, Kishida D, Uehara R, Nakamura Y, Jiuchi Y, Masumoto J, Furukawa H, Ida H, Terai C, Nakashima Y, Kawakami A, Nakamura T, Eguchi K, Yasunami M, Yachie A.
  • Journal Title: Medicine (Baltimore) Volume: 93 Issue: 3 Pages: 158-164
  • DOI: 10.1097/md.0000000000000029
  • Peer Reviewed
• [Journal Article] A case of colchicine-responsive Mollaret's meningitis with MEFV gene mutation. (2014)
  • Author(s): Kinohshita T, Matsushima A, Satoh S, Hoshi K, Kishida D, Yahikozawa H.
  • Journal Title: Rinsho Shinkeigaku. Volume: 54(2) Pages: 124-129
  • NAID: 130004505558
  • Peer Reviewed
• [Presentation] 中年期以降に発症した家族性地中海熱の臨床的特徴 (2017)
  • Author(s): 岸田大
  • Organizer: 第61回日本リウマチ学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2017-04-20
• [Presentation] 月経困難症として投与されたジエノゲストが有効性を示した家族性地中海熱の一例 (2016)
  • Author(s): 岸田大
  • Organizer: 第28回 日本リウマチ学会 中部支部学術集会
  • Place of Presentation: ザ・グランユアーズフクイ（福井県）
  • Year and Date: 2016-09-02
• [Presentation] 家族性地中海熱における発作と月経の関連 (2016)
  • Author(s): 岸田大
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
• [Presentation] 本邦における家族性地中海熱の臨床像と遺伝学的特徴 (2014)
  • Author(s): 岸田大
  • Organizer: 第59回 日本リウマチ学会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2014-04-23 – 2014-04-26
• [Remarks] 信州大学第三内科
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-3nai/
• [Remarks] 信州大学第三内科
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-3nai/theme11.html