Genetic analysis of susceptibility genes for osteoarthritis of the knee joing

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390417
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: MABUCHI Akihiko 東京大学, 大学院・医学系研究科, 准教授 (80312312)
• Co-Investigator(Kenkyū-buntansha): TOKUNAGA Katsushi 東京大学, 大学院・医学系研究科, 教授 (40163977) ; YOSHIMURA Noriko 東京大学, 医学部附属病院, 特任准教授 (60240355) ; AKUNE Tooru 東京大学, 医学部附属病院, 特任准教授 (60282662)
• Co-Investigator(Renkei-kenkyūsha): MURAKI Shigeyuki 東京大学, 医学部附属病院, 特任助教 (40401070) ; OKA Hiroyuki 東京大学, 医学部附属病院, 特任助教 (60401064)
• Project Period (FY): 2009 – 2011
• Keywords: 変形性関節症

Research Abstract

To investigate the underlying genetic variants in EPAS1 and MMP13 in osteoarthritis, we conducted a case-control association study in Japanese population. 475 patients and 563 health individuals from two areas(Itabashi and Miyama) of Japan were genotyped using restriction fragment length polymorphism and TaqMan SNP Genotyping Assays. The allele frequencies of rs1703192 in EPAS1 and rs2252070 in MMP13 were significantly different between knee osteoarthritis patients and healthy controls. In Itabashi cohort analysis, rs1703192 was associated with knee osteoarthritis under allelic(χ2test : p=0. 018) and recessive model(p=0. 031). In the cohorts-combined analysis, the associations were observed in rs1703192 under allelic(p=0. 013) and recessive(p=0. 018) models, and in rs2252070 under recessive model(p=0. 039).

Research Products

• [Journal Article] C/EBPβand RUNX2 cooperate to degrade cartilage with MMP13 as the target and HIF-2αas theinducer in chondrocytes (2012)
  • Author(s): Hirata M、Kugimiya F、Fukai A、Saito T、Yano F、Ikeda T、Mabuchi A、Sapkota BR、Akune T、Nishida N、Yoshimura N、NakagawaT、Tokunaga K、Nakamura K、Chung UI、Kawaguchi H
  • Journal Title: Human Molecular Genetics Volume: Vol.21 Pages: 1111-1123
  • DOI: DOI:10.1093/hmg/ddr540
  • Peer Reviewed
• [Journal Article] Translation Research in Europe Applied Technologies for Osteoarthritis(TreatOA)、Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22 (2011)
  • Author(s): Evangelou E、Valdes AM、Kerkhof HJ、Styrkarsdottir U、Zhu Y、Meulenbelt I、Lories RJ、Karassa FB、Tylzanowski P、Bos SD ; arcOGEN Consortium、Akune T、Arden NK、Carr A、Chapman K、Cupples LA、Dai J、Deloukas P、Doherty M、Doherty S、Engstrom G、Gonzalez A、Halldorsson BV、Hammond CL、Hart DJ、Helgadottir H、Hofman A、Ikegawa S、Ingvarsson T、Jiang Q、Jonsson H、Kaprio J、Kawaguchi H、Kisand K、Kloppenburg M、Kujala UM、Lohmander LS、Loughlin J、Luyten FP、Mabuchi A、McCaskie A、Nakajima M、Nilsson PM、Nishida N、Ollier WE、Panoutsopoulou K、van de Putte T、Ralston SH、Rivadeneira F、Saarela J、Schulte-Merker S、Shi D、Slagboom PE、Sudo A、Tamm A、Tamm A、Thorleifsson G、Thorsteinsdottir U、Tsezou A、Wallis GA、Wilkinson JM、Yoshimura N、Zeggini E、Zhai G、Zhang F、Jonsdottir I、Uitterlinden AG、Felson DT、van Meurs JB、Stefansson K、Ioannidis JP、Spector TD
  • Journal Title: Annals of the Rheumatic Diseses Volume: Vol.70 Pages: 349-355
  • DOI: DOI:10.1136/ard.2010.132787
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of endochondral ossification by HIF2A during skeletal growth and osteoarthritis development (2010)
  • Author(s): Saito T、Fukai A、Mabuchi A、Ikeda T、Yano F、Ohba S、Nishida N、Akune T、Yoshimura N、Nakagawa T、Nakamura K、Tokunaga K、Chung UI、Kawaguchi H
  • Journal Title: Nature Medicin Volume: Vol.16 Pages: 678-686
  • DOI: DOI:10.1038/nm.2146
  • Peer Reviewed