Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese.
作者： Feng Zhang , Yan Wen , Xiong Guo , Yingang Zhang , Xi Wang
DOI: 10.1002/ART.38898
关键词: Locus (genetics) 、 SNP array 、 Osteochondropathy 、 Single-nucleotide polymorphism 、 Genome-wide association study 、 SNP 、 Kashin–Beck disease 、 Genetics 、 Biology 、 Case-control study
摘要: Objective Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim this study was to identify susceptibility genes for KBD by conducting 2-stage genome-wide association (GWAS). Methods Ninety patients with grade II or III extreme phenotypes and 1,627 healthy control subjects were enrolled in initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 used genotyping. For replication study, 9 single-nucleotide polymorphisms (SNPs) significant gene identified GWAS (ITPR2) tested an independent validation sample composed 559 467 subjects. Results The (P = 1.58 × 10−8) between novel locus, ITPR2 rs10842750. showed associations at SNPs, including rs10842750 5.97 10−3), rs16931011 1.29 rs1531928 4.95 rs4414322 4.40 rs11048570 4.53 rs11048572 4.43 rs2017510 4.58 rs9669395 5.77 rs1002835 4.85 10−3). In KBD, genotype score also correlated clinical severity grades 0.013). Conclusion Our results strongly suggest that Han Chinese. This may provide new insights into rationale treatment as well other osteoarthritides similar articular cartilage lesions.
sci-hub.se 参考文章(18)
Leela Sedaghat, Natalia O. Glebova, Tomohiro Kurosaki, Solomon H. Snyder, Darren Boehning, Randen L. Patterson, Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nature Cell Biology. ,vol. 5, pp. 1051- 1061 ,(2003) , 10.1038/NCB1063
Zehua Chen, Gang Zheng, Kaushik Ghosh, Zhaohai Li, Linkage Disequilibrium Mapping of Quantitative-Trait Loci by Selective Genotyping American Journal of Human Genetics. ,vol. 77, pp. 661- 669 ,(2005) , 10.1086/491658
T. Szado, V. Vanderheyden, J. B. Parys, H. De Smedt, K. Rietdorf, L. Kotelevets, E. Chastre, F. Khan, U. Landegren, O. Soderberg, M. D. Bootman, H. L. Roderick, Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 2427- 2432 ,(2008) , 10.1073/PNAS.0711324105
Darren Boehning, Randen L. Patterson, Solomon H. Snyder, Apoptosis and calcium: new roles for cytochrome c and inositol 1,4,5-trisphosphate. Cell Cycle. ,vol. 3, pp. 252- 254 ,(2004) , 10.4161/CC.3.3.705
Yi Shi, Fang Lu, Xin Liu, Yao Wang, Lulin Huang, Xiaoqi Liu, Wubin Long, Bo Lv, Kun Zhang, Shi Ma, He Lin, Jing Cheng, Bin Zhou, Mei Hu, Jiayun Deng, Jianxin Zhu, Peng Hao, Xiao Yang, Mingcai Zeng, Xiaoquan Wang, Sikui Shen, Zhenglin Yang, Genetic variants in the HLA–DRB1 gene are associated with Kashin‐Beck disease in the Tibetan population Arthritis & Rheumatism. ,vol. 63, pp. 3408- 3416 ,(2011) , 10.1002/ART.30526
Gábor Szalai, Rajeshwari Krishnamurthy, György Hajnóczky, Apoptosis driven by IP(3)-linked mitochondrial calcium signals. The EMBO Journal. ,vol. 18, pp. 6349- 6361 ,(1999) , 10.1093/EMBOJ/18.22.6349
J.T. Liu, X. Guo, W.J. Ma, Y.G. Zhang, P. Xu, J.F. Yao, Y.D. Bai, Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin–Beck disease Osteoarthritis and Cartilage. ,vol. 18, pp. 1218- 1226 ,(2010) , 10.1016/J.JOCA.2010.07.003
Yoshinari Miyamoto, Dongquan Shi, Masahiro Nakajima, Kouichi Ozaki, Akihiro Sudo, Akihiro Kotani, Atsumasa Uchida, Toshihiro Tanaka, Naoshi Fukui, Tatsuhiko Tsunoda, Atsushi Takahashi, Yusuke Nakamura, Qing Jiang, Shiro Ikegawa, Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis Nature Genetics. ,vol. 40, pp. 994- 998 ,(2008) , 10.1038/NG.176
A. M. Valdes, E. Evangelou, H. J. M. Kerkhof, A. Tamm, S. A. Doherty, K. Kisand, A. Tamm, I. Kerna, A. Uitterlinden, A. Hofman, F. Rivadeneira, C. Cooper, E. M. Dennison, W. Zhang, K. R. Muir, J. P. A. Ioannidis, M. Wheeler, R. A. Maciewicz, J. B. van Meurs, N. K. Arden, T. D. Spector, M. Doherty, The GDF5 rs143383 polymorphism is associated with osteoarthritis of the knee with genome-wide statistical significance Annals of the Rheumatic Diseases. ,vol. 70, pp. 873- 875 ,(2011) , 10.1136/ARD.2010.134155
Michael A van Es, Paul W Van Vught, Hylke M Blauw, Lude Franke, Christiaan G Saris, Peter M Andersen, Ludo Van Den Bosch, Sonja W de Jong, Ruben van 't Slot, Anna Birve, Robin Lemmens, Vianney de Jong, Frank Baas, Helenius J Schelhaas, Kristel Sleegers, Christine Van Broeckhoven, John HJ Wokke, Cisca Wijmenga, Wim Robberecht, Jan H Veldink, Roel A Ophoff, Leonard H van den Berg, ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study Lancet Neurology. ,vol. 6, pp. 869- 877 ,(2007) , 10.1016/S1474-4422(07)70222-3