ゲノムワイド関連解析による関節リウマチ重症化遺伝子同定とその臨床応用への基盤整備

2011 年度 研究成果報告書

• 研究課題/領域番号: 20689029
• 研究種目: 若手研究(A)
• 配分区分: 補助金
• 研究分野: 整形外科学
• 研究機関: 東京女子医科大学
• 研究代表者: 猪狩 勝則 東京女子医科大学, 医学部, 准教授 (80343557)
• 研究期間 (年度): 2008 – 2011
• キーワード: リウマチ病学

研究概要

ゲノムワイド関連解析(GWAS)を用い、まず関節リウマチ(RA)の疾患感受性遺伝子の同定を試みた。単独のGWASでは既知の疾患感受性領域であるHLAが同定されたのみだったが、多施設共同研究でのメタ解析により9つの新規疾患感受性領域を同定し、他に14の既知の疾患感受性遺伝子領域での関連を確認した。ゲノムワイド水準を超える関連を認める疾患重症化領域はなかったが、HLA-DRB1とPADI4での関連を確認した。

研究成果

• [雑誌論文] Quantitative effect of HLA-DRB1 alleles to ACPA levels in Japanese rheumatoid arthritis : no strong genetic impact of shared epitope to ACPA levels after stratification of HLA-DRB1 09 : 01 (2012)
  • 著者名/発表者名: Terao C, Ikari K, Ohmura K, Suzuki T, Iwamoto T, Takasugi K, Saji H, Taniguchi A, Momohara S, Yamanaka H, Matsuda F, Mimori T
  • 雑誌名: Annals of the rheumatic diseases 巻: 71(6) ページ: 1095-7
• [雑誌論文] Non-synonymous variant(Gly307Ser) in CD226 is associated with susceptibility in Japanese rheumatoid arthritis patients (2012)
  • 著者名/発表者名: Suzuki T, Ikari K, Kawaguchi Y, Yano K, Iwamoto T, Kawamoto M, Toyama Y, Taniguchi A, Yamanaka H, Momohara S
  • 雑誌名: Modern rheumatology 巻: (in press)
• [雑誌論文] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population (2012)
  • 著者名/発表者名: Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K
  • 雑誌名: Nature genetics 巻: 44(5) ページ: 511-6
• [雑誌論文] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese (2012)
  • 著者名/発表者名: Okada Y, Shimane K, Kochi Y, Tahira T, Suzuki A, Higasa K, Takahashi A, Horita T, Atsumi T, Ishii T, Okamoto A, Fujio K, Hirakata M, Amano H, Kondo Y, Ito S, Takada K, Mimori A, Saito K, Kamachi M, Kawaguchi Y, Ikari K, Mohammed OW, Matsuda K, Terao C, Ohmura K, Myouzen K, Hosono N, Tsunoda T, Nishimoto N, Mimori T, Matsuda F, Tanaka Y, Sumida T, Yamanaka H, Takasaki Y, Koike T, Horiuchi T, Hayashi K, Kubo M, Kamatani N, Yamada R, Nakamura Y, Yamamoto K
  • 雑誌名: PLoS genetics 巻: 8(1) ページ: e1002455
• [雑誌論文] Comparison of characteristics and therapeutic efficacy in rheumatoid arthritis patients treated by rheumatologists and those treated by orthopedic surgeons under a team medicine approach at the same institute (2012)
  • 著者名/発表者名: Momohara S, Inoue E, Ikari K, Yano K, Tokita A, Honjo Y, Sakuma Y, Hiroshima R, Iwamoto T, Seto Y, Tanaka E, Taniguchi A, Yamanaka H
  • 雑誌名: Modern rheumatology 巻: 22(2) ページ: 209-15
• [雑誌論文] A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects (2011)
  • 著者名/発表者名: Terao C, Ohmura K, Kochi Y, Ikari K, Maruya E, Katayama M, Shimada K, Murasawa A, Honjo S, Takasugi K, Matsuo K, Tajima K, Suzuki A, Yamamoto K, Momohara S, Yamanaka H, Yamada R, Saji H, Matsuda F, Mimori T
  • 雑誌名: Annals of the rheumatic diseases 巻: 70(12) ページ: 2134-9
• [雑誌論文] Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis : protective effect of the T allele and T/T genotype at rs360722 (2011)
  • 著者名/発表者名: Sugiura T, Kawaguchi Y, Ikari K, Ichida H, Kawamoto M, Momohara S, Hara M, Yamanaka H
  • 雑誌名: Modern rheumatology 巻: 21(4) ページ: 359-64
• [雑誌論文] Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population (2011)
  • 著者名/発表者名: Nishimoto K, Ikari K, Kaneko H, Tsukahara S, Kochi Y, Yamamoto K, Nakamura Y, Toyama Y, Taniguchi A, Yamanaka H, Momohara S
  • 雑誌名: The Journal of rheumatology 巻: 38(2) ページ: 221-8
• [雑誌論文] Recent trends in orthopedic surgery performed in Japan for rheumatoid arthritis (2011)
  • 著者名/発表者名: Momohara S, Tanaka S, Nakamura H, Mibe J, Iwamoto T, Ikari K, Nishino J, Kadono Y, Yasui T, Takahashi K, Takenouchi K, Hashizume K, Nakahara R, Kubota A, Nakamura T, Nishida K, Suguro T
  • 雑誌名: Modern rheumatology 巻: 21(4) ページ: 337-42
• [雑誌論文] Reparative radiological changes of a large joint after adalimumab for rheumatoid arthritis (2011)
  • 著者名/発表者名: Momohara S, Tanaka E, Iwamoto T, Ikari K, Yamanaka H
  • 雑誌名: Clinical rheumatology 巻: 30(4) ページ: 591-2
• [雑誌論文] Prosthetic joint infection after total hip or knee arthroplasty in rheumatoid arthritis patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs (2011)
  • 著者名/発表者名: Momohara S, Kawakami K, Iwamoto T, Yano K, Sakuma Y, Hiroshima R, Imamura H, Masuda I, Tokita A, Ikari K
  • 雑誌名: Modern rheumatology 巻: 21(5) ページ: 469-75
• [雑誌論文] Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis : improved longitudinal effects on disease activity but not on health-related quality of life (2011)
  • 著者名/発表者名: Momohara S, Inoue E, Ikari K, Yano K, Tokita A, Suzuki T, Sakuma Y, Hiroshima R, Kawakami K, Masuda I, Iwamoto T, Taniguchi A, Yamanaka H
  • 雑誌名: Modern rheumatology 巻: 21(5) ページ: 476-81
• [雑誌論文] The increasing disease duration of patients at the time of orthopaedic surgery for rheumatoid arthritis (2011)
  • 著者名/発表者名: Momohara S, Ikari K, Kawakami K, Iwamoto T, Inoue E, Yano K, Sakuma Y, Hiroshima R, Tokita A, Taniguchi A, Yamanaka H
  • 雑誌名: Rheumatology international
• [雑誌論文] Clinical images : Solitary extranodal malignant lymphoma of the forearm in rheumatoid arthritis (2011)
  • 著者名/発表者名: Iwamoto T, Seto Y, Ikari K, Yamanaka H, Momohara S
  • 雑誌名: Arthritis and rheumatism 巻: 63(1) ページ: 304
• [雑誌論文] Pseudotumor from a metal-on-metal hip (2011)
  • 著者名/発表者名: Iwamoto T, Ikari K, Momohara S
  • 雑誌名: The Journal of rheumatology 巻: 38(10) ページ: 2265
• [雑誌論文] Analysis of C-reactive protein levels and febrile tendency after joint surgery in rheumatoid arthritis patients treated with a perioperative 4-week interruption of tocilizumab (2011)
  • 著者名/発表者名: Hiroshima R, Kawakami K, Iwamoto T, Tokita A, Yano K, Sakuma Y, Ikari K, Momohara S
  • 雑誌名: Modern rheumatology 巻: 21(1) ページ: 109-11
• [雑誌論文] Effect of total knee arthroplasty on disease activity in patients with established rheumatoid arthritis : 3-year follow-up results of combined medical therapy and surgical intervention (2010)
  • 著者名/発表者名: Yano K, Ikari K, Inoue E, Tokita A, Sakuma Y, Hiroshima R, Iwamoto T, Kawakami K, Taniguchi A, Yamanaka H, Momohara S
  • 雑誌名: Modern rheumatology 巻: 20(5) ページ: 452-7
• [雑誌論文] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population (2010)
  • 著者名/発表者名: Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K
  • 雑誌名: Arthritis and rheumatism 巻: 62(2) ページ: 574-9
• [雑誌論文] Reparative radiological changes of the hip joint in rheumatoid arthritis : do these findings indicate the true repair of the joint (2010)
  • 著者名/発表者名: Sakuma Y, Ikari K, Iwamoto T, Tokita A, Momohara S
  • 雑誌名: Joint, bone, spine : revue du rhumatisme. 巻: 77(3) ページ: 278-9
• [雑誌論文] Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus (2010)
  • 著者名/発表者名: Ota Y, Kawaguchi Y, Takagi K, Tochimoto A, Kawamoto M, Katsumata Y, Gono T, Masuda I, Ikari K, Momohara S, Yamanaka H
  • 雑誌名: Modern rheumatology 巻: 20(5) ページ: 427-31
• [雑誌論文] Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese (2010)
  • 著者名/発表者名: Nishimoto K, Kochi Y, Ikari K, Yamamoto K, Suzuki A, Shimane K, Nakamura Y, Yano K, Iikuni N, Tsukahara S, Kamatani N, Okamoto H, Kaneko H, Kawaguchi Y, Hara M, Toyama Y, Horiuchi T, Tao K, Yasutomo K, Hamada D, Yasui N, Inoue H, Itakura M, Yamanaka H, Momohara S
  • 雑誌名: Annals of the rheumatic diseases 巻: 69(2) ページ: 368-73
• [雑誌論文] Decrease in orthopaedic operations, including total joint replacements, in patients with rheumatoid arthritis between 2001 and 2007 : data from Japanese outpatients in a single institute-based large observational cohort(IORRA) (2010)
  • 著者名/発表者名: Momohara S, Inoue E, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Hara M, Taniguchi A, Yamanaka H
  • 雑誌名: Annals of the rheumatic diseases 巻: 69(1) ページ: 312-3
• [雑誌論文] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility (2010)
  • 著者名/発表者名: Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K
  • 雑誌名: Nature genetics 巻: 42(6) ページ: 515-9
• [雑誌論文] Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers : perioperative interruption of tumour necrosis factor-alpha blockers decreases complications (2010)
  • 著者名/発表者名: Kawakami K, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Yano K, Sakuma Y, Tokita A, Momohara S
  • 雑誌名: Rheumatology(Oxford) 巻: 49(2) ページ: 341-7
• [雑誌論文] Multiple extensor tendon ruptures caused by tophaceous gout (2010)
  • 著者名/発表者名: Iwamoto T, Toki H, Ikari K, Yamanaka H, Momohara S
  • 雑誌名: Modern rheumatology 巻: 20(2) ページ: 210-2
• [雑誌論文] A thought on postgraduate psychiatric education from the viewpoint of residents in the latter stage of training based on the system of training of psychiatric specialists-the latter part of the psychiatric training at university hospitals (2009)
  • 著者名/発表者名: Nakano W, Kato T, Tateno M, Ikari K, Tanaka T, Nakamae T, Hojusan T, Nakamura J
  • 雑誌名: Seishin shinkeigaku zasshi=Psychiatria et neurologia Japonica 巻: 111(10) ページ: 1214-9
• [雑誌論文] Declining use of synovectomy surgery for patients with rheumatoid arthritis in Japan (2009)
  • 著者名/発表者名: Momohara S, Ikari K, Mochizuki T, Kawamura K, Tsukahara S, Toki H, Hara M, Kamatani N, Yamanaka H, Tomatsu T
  • 雑誌名: Annals of the rheumatic diseases 巻: 68(2) ページ: 291-2
• [雑誌論文] Clinical image : adductor muscle strain in an elderly patient with suspected femoral neck fracture (2009)
  • 著者名/発表者名: Kawakami K, Ikari K, Yano K, Momohara S
  • 雑誌名: Arthritis and rheumatism 巻: 60(11) ページ: 3446
• [雑誌論文] A1330V polymorphism of low-density lipoprotein receptor-related protein 5 gene and self-reported incident fractures in Japanese female patients with rheumatoid arthritis (2009)
  • 著者名/発表者名: Furuya T, Urano T, Ikari K, Kotake S, Inoue S, Hara M, Momohara S, Kamatani N, Yamanaka H
  • 雑誌名: Modern rheumatology 巻: 19(2) ページ: 140-6
• [雑誌論文] Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients (2008)
  • 著者名/発表者名: Tsukahara S, Shinozaki M, Ikari K, Mochizuki T, Inoue E, Tomatsu T, Hara M, Yamanaka H, Kamatani N, Momohara S
  • 雑誌名: Rheumatology(Oxford) 巻: 47(1) ページ: 41-4
• [雑誌論文] CTLA-4 CT60 polymorphism is not an independent genetic risk marker of rheumatoid arthritis in a Japanese population (2008)
  • 著者名/発表者名: Tsukahara S, Iwamoto T, Ikari K, Inoue E, Tomatsu T, Hara M, Yamanaka H, Kamatani N, Momohara S
  • 雑誌名: Annals of the rheumatic diseases 巻: 67(3) ページ: 428-9
• [雑誌論文] A polymorphism in the gene encoding the Fcgamma IIIA receptor is a possible genetic marker to predict the primary response to infliximab in Japanese patients with rheumatoid arthritis (2008)
  • 著者名/発表者名: Tsukahara S, Ikari K, Sato E, Yamanaka H, Hara M, Tomatsu T, Momohara S, Kamatani N
  • 雑誌名: Annals of the rheumatic diseases 巻: 67(12) ページ: 1791-2
• [雑誌論文] Iliopsoas bursitis-associated femoral neuropathy exacerbated after internal fixation of an intertrochanteric hip fracture in rheumatoid arthritis : a case report (2008)
  • 著者名/発表者名: Tokita A, Ikari K, Tsukahara S, Toki H, Miyawaki M, Mochizuki T, Kawamura K, Tomatsu T, Momohara S
  • 雑誌名: Modern rheumatology 巻: 18(4) ページ: 394-8
• [雑誌論文] Infusion reaction to infliximab in a patient with rheumatoid arthritis after discontinuation over 1 year and readministration (2008)
  • 著者名/発表者名: Toki H, Momohara S, Tsukahara S, Ikari K
  • 雑誌名: The Journal of rheumatology 巻: 35(9) ページ: 1896-7
• [雑誌論文] Return of infliximab efficacy after total knee arthroplasty in a patient with rheumatoid arthritis (2008)
  • 著者名/発表者名: Toki H, Momohara S, Ikari K, Kawamura K, Tsukahara S, Mochizuki T, Sato E, Yamanaka H
  • 雑誌名: Clinical rheumatology 巻: 27(4) ページ: 549-50
• [雑誌論文] Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan : one-year outcome of joint destruction(RECONFIRM-2J) (2008)
  • 著者名/発表者名: Takeuchi T, Yamanaka H, Inoue E, Nagasawa H, Nawata M, Ikari K, Saito K, Sekiguchi N, Sato E, Kameda H, Iwata S, Mochizuki T, Amano K, Tanaka Y.
  • 雑誌名: Modern rheumatology 巻: 18(5) ページ: 447-54
• [雑誌論文] Lack of association between PADI4 and functional severity in Japanese rheumatoid arthritis patients (2008)
  • 著者名/発表者名: Nishimoto K, Ikari K, Mochizuki T, Tomatsu T, Toyama Y, Hara M, Yamanaka H, Kamatani N, Momohara S
  • 雑誌名: Annals of the rheumatic diseases 巻: 67(3) ページ: 431-2
• [雑誌論文] Risk factors for wrist surgery in rheumatoid arthritis (2008)
  • 著者名/発表者名: Momohara S, Inoue E, Ikari K, Tsukahara S, Kawamura K, Toki H, Hara M, Kamatani N, Yamanaka H, Tomatsu T
  • 雑誌名: Clinical rheumatology 巻: 27(11) ページ: 1387-91
• [雑誌論文] Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population (2008)
  • 著者名/発表者名: Kobayashi S, Ikari K, Kaneko H, Kochi Y, Yamamoto K, Shimane K, Nakamura Y, Toyama Y, Mochizuki T, Tsukahara S, Kawaguchi Y, Terai C, Hara M, Tomatsu T, Yamanaka H, Horiuchi T, Tao K, Yasutomo K, Hamada D, Yasui N, Inoue H, Itakura M, Okamoto H, Kamatani N, Momohara S
  • 雑誌名: Arthritis and rheumatism 巻: 58(7) ページ: 1940-6
• [雑誌論文] Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese (2008)
  • 著者名/発表者名: Furuichi T, Maeda K, Chou CT, Liu YF, Liu TC, Miyamoto Y, Takahashi A, Mori K, Ikari K, Kamatani N, Kurosawa H, Inoue H, Tsai SF, Ikegawa S
  • 雑誌名: Journal of human genetics 巻: 53(5) ページ: 419-24
• [備考]
  • URL: http://www.twmu.ac.jp/IOR/JointSurgery/