Replication studies in various ethnic populations do not support the association of the hif-2α snp rs17039192 with knee osteoarthritis

Replication studies in various ethnic populations do not support the association of the hif-2α snp rs17039192 with knee osteoarthritis

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Access through your institution Buy or subscribe To the Editor: We read with great interest the recent article in _Nature Medicine_ by Saito et al.1 describing the role of hypoxia-inducible factor-2α (HIF-2α) in skeletal growth and osteoarthritis development. The authors report that HIF-2α is a central transactivator targeting several crucial genes for endochondral ossification in mice1. The role of HIF-2α in human osteoarthritis is buttressed by their Japanese association study suggesting that rs17039192, a functional single nucleotide polymorphism (SNP) in the human _EPAS1_ gene encoding HIF-2α, is associated with knee osteoarthritis1. Although the study clearly contains interesting and compelling data on the effect of HIF-2α in endochondral ossification during skeletal growth in mice, the human evidence, supporting the role of HIF-2α in osteoarthritis, is limited by its small sample size and a marginal _P_ value. Given that lack of replication and false positive findings are common pitfalls of association studies2, we sought to further clarify the association of the HIF-2α SNP rs17039192 with osteoarthritis. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Saito, T. et al. _Nat. Med._ 16, 641–644 (2010). Article  Google Scholar  * Ikegawa, S. _Curr. Opin. Rheumatol._ 19, 429–434 (2007). Article  Google Scholar  * Miyamoto, Y. et al. _Nat. Genet._ 39, 529–533 (2007). Article  CAS  Google Scholar  * Nakajima, M. et al. _PLoS One_ 18, e9723 (2010). Article  Google Scholar  * Shi, D. et al. _Osteoarthritis Cartilage_ 18, 1454–1457 (2010). Article  CAS  Google Scholar  * Yang, S. et al. _Nat. Med._ 16, 687–693 (2010). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION Author notes * Masahiro Nakajima and Dongquan Shi: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan Masahiro Nakajima, Jin Dai & Shiro Ikegawa * The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China Dongquan Shi, Jin Dai & Qing Jiang * Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, China Dongquan Shi, Shiro Ikegawa & Qing Jiang * Laboratory of Cytogenetics and Molecular Genetics, Medical School, University of Thessaly, Larissa, Greece Aspasia Tsezou * School of Surgery, University of Western Australia, Perth, Australia Minghao Zheng, Paul E Norman & Shiro Ikegawa * Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan Atsushi Takahashi Authors * Masahiro Nakajima View author publications You can also search for this author inPubMed Google Scholar * Dongquan Shi View author publications You can also search for this author inPubMed Google Scholar * Jin Dai View author publications You can also search for this author inPubMed Google Scholar * Aspasia Tsezou View author publications You can also search for this author inPubMed Google Scholar * Minghao Zheng View author publications You can also search for this author inPubMed Google Scholar * Paul E Norman View author publications You can also search for this author inPubMed Google Scholar * Atsushi Takahashi View author publications You can also search for this author inPubMed Google Scholar * Shiro Ikegawa View author publications You can also search for this author inPubMed Google Scholar * Qing Jiang View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Shiro Ikegawa or Qing Jiang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Fig. 1 and Supplementary Table 1 (PDF 107 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nakajima, M., Shi, D., Dai, J. _et al._ Replication studies in various ethnic populations do not support the association of the HIF-2α SNP rs17039192 with knee osteoarthritis. _Nat Med_ 17, 26–27 (2011). https://doi.org/10.1038/nm0111-26 Download citation * Published: 07 January 2011 * Issue Date: January 2011 * DOI: https://doi.org/10.1038/nm0111-26 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

Access through your institution Buy or subscribe To the Editor: We read with great interest the recent article in _Nature Medicine_ by Saito et al.1 describing the role of hypoxia-inducible


factor-2α (HIF-2α) in skeletal growth and osteoarthritis development. The authors report that HIF-2α is a central transactivator targeting several crucial genes for endochondral ossification


in mice1. The role of HIF-2α in human osteoarthritis is buttressed by their Japanese association study suggesting that rs17039192, a functional single nucleotide polymorphism (SNP) in the


human _EPAS1_ gene encoding HIF-2α, is associated with knee osteoarthritis1. Although the study clearly contains interesting and compelling data on the effect of HIF-2α in endochondral


ossification during skeletal growth in mice, the human evidence, supporting the role of HIF-2α in osteoarthritis, is limited by its small sample size and a marginal _P_ value. Given that


lack of replication and false positive findings are common pitfalls of association studies2, we sought to further clarify the association of the HIF-2α SNP rs17039192 with osteoarthritis.


This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access


$209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are


calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Saito, T. et al. _Nat. Med._


16, 641–644 (2010). Article  Google Scholar  * Ikegawa, S. _Curr. Opin. Rheumatol._ 19, 429–434 (2007). Article  Google Scholar  * Miyamoto, Y. et al. _Nat. Genet._ 39, 529–533 (2007).


Article  CAS  Google Scholar  * Nakajima, M. et al. _PLoS One_ 18, e9723 (2010). Article  Google Scholar  * Shi, D. et al. _Osteoarthritis Cartilage_ 18, 1454–1457 (2010). Article  CAS 


Google Scholar  * Yang, S. et al. _Nat. Med._ 16, 687–693 (2010). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION Author notes * Masahiro Nakajima and Dongquan Shi:


These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan Masahiro Nakajima, Jin Dai


 & Shiro Ikegawa * The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China Dongquan Shi, Jin Dai 


& Qing Jiang * Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, China Dongquan Shi, Shiro Ikegawa & Qing Jiang * Laboratory of


Cytogenetics and Molecular Genetics, Medical School, University of Thessaly, Larissa, Greece Aspasia Tsezou * School of Surgery, University of Western Australia, Perth, Australia Minghao


Zheng, Paul E Norman & Shiro Ikegawa * Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan Atsushi Takahashi Authors * Masahiro Nakajima View author


publications You can also search for this author inPubMed Google Scholar * Dongquan Shi View author publications You can also search for this author inPubMed Google Scholar * Jin Dai View


author publications You can also search for this author inPubMed Google Scholar * Aspasia Tsezou View author publications You can also search for this author inPubMed Google Scholar *


Minghao Zheng View author publications You can also search for this author inPubMed Google Scholar * Paul E Norman View author publications You can also search for this author inPubMed 


Google Scholar * Atsushi Takahashi View author publications You can also search for this author inPubMed Google Scholar * Shiro Ikegawa View author publications You can also search for this


author inPubMed Google Scholar * Qing Jiang View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Shiro Ikegawa or Qing


Jiang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Fig. 1 and


Supplementary Table 1 (PDF 107 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nakajima, M., Shi, D., Dai, J. _et al._ Replication studies in various


ethnic populations do not support the association of the HIF-2α SNP rs17039192 with knee osteoarthritis. _Nat Med_ 17, 26–27 (2011). https://doi.org/10.1038/nm0111-26 Download citation *


Published: 07 January 2011 * Issue Date: January 2011 * DOI: https://doi.org/10.1038/nm0111-26 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content:


Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative