Genome-wide association study of non-vertebral fractures in patients with rheumatoid arthritis

• Project/Area Number: 15H04965
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ikari Katsunori 東京女子医科大学, 医学部, 准教授 (80343557)
• Research Collaborator: SHIMAZAKI Miwako 東京女子医科大学, 医学部, 初期研修医
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2015: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 関節リウマチ / 骨折 / 遺伝子 / ゲノム

Outline of Final Research Achievements

Patients with rheumatoid arthritis (RA) are predisposed to having fracture. We tried to detect genetic risk factors for having non-vertebral fractures in relation to gender, age, disease activity and the other environmental factors. Clinical data were collected from the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) cohort study that included more than 10,000 patients with RA from October 2000 to May 2015. Among them, a whole genome SNP genotyping by DNA microarray was conducted in more than 3,000 patients.. The statistical analyses including quality controls was evaluated using the PLINK software. We also studied the risk factors for fall that is associated with fracture, physical functions of the patients, and clinical studies of treating osteoporosis in patients with RA. The studies had successful results and we have to push forward with our future study plans on RA.

Research Products

• [Journal Article] HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies (2018)
  • Author(s): Hiwa Ryosuke、Ikari Katsunori、Ohmura Koichiro、Nakabo Shuichiro、Matsuo Keitaro、Saji Hiroh、Yurugi Kimiko、Miura Yasuo、Maekawa Taira、Taniguchi Atsuo、Yamanaka Hisashi、Matsuda Fumihiko、Mimori Tsuneyo、Terao Chikashi
  • Journal Title: The Journal of Rheumatology Volume: 45 Issue: 4 Pages: 470-480
  • DOI: 10.3899/jrheum.170363
  • Peer Reviewed
• [Journal Article] Genetic landscape of interactive effects ofHLA-DRB1alleles on susceptibility to ACPA(+) rheumatoid arthritis and ACPA levels in Japanese population (2017)
  • Author(s): Terao Chikashi、Okada Yukinori、Ikari Katsunori、Kochi Yuta、Suzuki Akari、Ohmura Koichiro、Matsuo Keitaro、Taniguchi Atsuo、Kubo Michiaki、Raychaudhuri Soumya、Yamamoto Kazuhiko、Yamanaka Hisashi、Kamatani Yoichiro、Mimori Tsuneyo、Matsuda Fumihiko
  • Journal Title: Journal of Medical Genetics Volume: 54 Issue: 12 Pages: 853-858
  • DOI: 10.1136/jmedgenet-2017-104779
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head (2017)
  • Author(s): Sakamoto Y, Yamamoto T, Sugano N, Takahashi D, Watanabe T, Atsumi T, Nakamura J, Hasegawa Y, Akashi K, Narita I, Miyamoto T, Takeuchi T, Ikari K, Amano K, Fujie A, Kubo T, Tada Y, Kaneuji A, Nakamura H, Miyamura T, Kabata T, Yamaji K, Okawa T, Sudo A, Ohzono K, Tanaka Y, Yasunaga Y, Matsuda S, Imai Y
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 15035-15035
  • DOI: 10.1038/s41598-017-14778-y
  • NAID: 120006817606
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between achievement of physical activity goal and characteristics of patients with rheumatoid arthritis (2017)
  • Author(s): Mochizuki Takeshi、Yano Koichiro、Ikari Katsunori、Kawakami Kosei、Hiroshima Ryo、Momohara Shigeki
  • Journal Title: Modern Rheumatology Volume: - Issue: 4 Pages: 606-610
  • DOI: 10.1080/14397595.2017.1371104
  • Peer Reviewed
• [Journal Article] Correlation between hand bone mineral density and joint destruction in established rheumatoid arthritis (2017)
  • Author(s): Mochizuki Takeshi、Yano Koichiro、Ikari Katsunori、Hiroshima Ryo、Sakuma Yu、Momohara Shigeki
  • Journal Title: Journal of Orthopaedics Volume: 14 Issue: 4 Pages: 461-465
  • DOI: 10.1016/j.jor.2017.07.010
  • Peer Reviewed
• [Journal Article] Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis. (2017)
  • Author(s): Kuramoto N, Ohmura K, Ikari K, Yano K, Furu M, Yamakawa N, Hashimoto M, Ito H, Fujii T, Murakami K, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Taniguchi A, Momohara S, Yamanaka H, Matsuda F, Mimori T, Terao C
  • Journal Title: Sc Rep Volume: 7 Issue: 1 Pages: 6911-6911
  • DOI: 10.1038/s41598-017-07137-4
  • NAID: 120006368159
  • Peer Reviewed / Open Access
• [Journal Article] Time-averaged disease activity fits better joint destruction in rheumatoid arthritis (2017)
  • Author(s): Tsuji Hideaki、Yano Koichiro、Furu Moritoshi、Yamakawa Noriyuki、Ikari Katsunori、Hashimoto Motomu、Ito Hiromu、Fujii Takao、Yamamoto Wataru、Ohmura Koichiro、Taniguchi Atsuo、Momohara Shigeki、Matsuda Fumihiko、Allaart Cornelia F.、Yamanaka Hisashi、Mimori Tsuneyo、Terao Chikashi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 5856-5856
  • DOI: 10.1038/s41598-017-05581-w
  • NAID: 120006366785
  • Peer Reviewed / Open Access
• [Journal Article] Effects of denosumab treatment on bone mineral density and joint destruction in patients with rheumatoid arthritis (2017)
  • Author(s): Mochizuki Takeshi、Yano Koichiro、Ikari Katsunori、Kawakami Kosei、Hiroshima Ryo、Koenuma Naoko、Ishibashi Mina、Momohara Shigeki
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: - Issue: 4 Pages: 431-438
  • DOI: 10.1007/s00774-017-0848-1
  • Peer Reviewed
• [Journal Article] Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis (2017)
  • Author(s): Ishigaki Kazuyoshi、Kochi Yuta、Suzuki Akari、Tsuchida Yumi、Tsuchiya Haruka、Sumitomo Shuji、Yamaguchi Kensuke、Nagafuchi Yasuo、Nakachi Shinichiro、Kato Rika、Sakurai Keiichi、Shoda Hirofumi、Ikari Katsunori、Taniguchi Atsuo、Yamanaka Hisashi、Miya Fuyuki、Tsunoda Tatsuhiko、et al.、Yamamoto Kazuhiko
  • Journal Title: Nature Genetics Volume: 49 Issue: 7 Pages: 1120-1125
  • DOI: 10.1038/ng.3885
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The minimally important difference for the Japanese version of the health assessment questionnaire in patients with rheumatoid arthritis in daily practice. (2017)
  • Author(s): Shidara K, Nakajima A, Inoue E, Hoshi D, Sugimoto N, Seto Y, Tanaka E, Ikari K, Taniguchi A, Yamanaka H.
  • Journal Title: Mod Rheumatol. Volume: - Issue: 3 Pages: 430-434
  • DOI: 10.1080/14397595.2016.1213490
• [Journal Article] A twin study of rheumatoid arthritis in the Japanese population (2016)
  • Author(s): Terao, C., Ikari, K., Nakayamada, S., Takahashi, Y., Yamada, R., Ohmura, K., Hashimoto, M., Furu, M., Ito, H., Fujii, T., Yoshida, S., Saito, K., Taniguchi, A., Momohara, S., Yamanaka, H., Mimori, T., & Matsuda, F.
  • Journal Title: Modern Rheumatology Volume: 印刷中 Issue: 5 Pages: 685-689
  • DOI: 10.3109/14397595.2015.1135856
  • Peer Reviewed
• [Journal Article] Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis (2016)
  • Author(s): Okada Y, Suzuki A, Ikari K, Terao C, Kochi Y, Ohmura K, Higasa K, Akiyama M, Ashikawa K, Kanai M, Hirata J, Suita N, Teo YY, Xu H, Bae SC, Takahashi A, Momozawa Y, Matsuda K, Momohara S, Taniguchi A, Yamada R, Mimori T, Kubo M, Brown MA, Raychaudhuri S, Matsuda F, Yamanaka H, Kamatani Y, Yamamoto K
  • Journal Title: Am J Hum Genet Volume: 99 Issue: 2 Pages: 366-374
  • DOI: 10.1016/j.ajhg.2016.06.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line (2016)
  • Author(s): Imamura H, YoshinaS, Ikari K, Miyazawa K, Momohara S, Mitani S
  • Journal Title: Mod Rheumatol Volume: - Issue: 4 Pages: 1-10
  • DOI: 10.3109/14397595.2015.1112481
  • NAID: 120007144512
  • Peer Reviewed / Open Access
• [Journal Article] Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis. (2016)
  • Author(s): Kim K, Bang SY, Ikari K, Yoo DH, Cho SK, Choi CB, Sung YK, Kim TH, Jun JB, Kang YM, Suh CH, Shim SC, Lee SS, Lee J, Chung WT, Kim SK, Choe JY, Momohara S, Taniguchi A, Yamanaka H, Nath SK, Lee HS, Bae SC.
  • Journal Title: Sci Rep. Volume: - Issue: 1
  • DOI: 10.1038/srep27563
  • Peer Reviewed / Open Access