Association of the Tag SNPs in the Human SKT Gene (KIAA1217) With Lumbar Disc Herniation |
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| Authors: | Tatsuki Karasugi Kei Semba Yuichiro Hirose Anthi Kelempisioti Masahiro Nakajima Atsushi Miyake Tatsuya Furuichi Yoshiharu Kawaguchi Yasuo Mikami Kazuhiro Chiba Michihiro Kamata Kouichi Ozaki Atsushi Takahashi Pirkka Mäkelä Jaro Karppinen Tomoatsu Kimura Toshikazu Kubo Yoshiaki Toyama Ken‐ichi Yamamura Minna Männikkö Hiroshi Mizuta Shiro Ikegawa MD PhD |
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| Institution: | 1. Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan;2. Department of Orthopaedic and Neuro‐Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan;3. Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan;4. Oulu Center for Cell ‐Matrix Research, Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, Oulu, Finland;5. Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan;6. Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;7. Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, Kanagawa, Japan;8. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan;9. Department of Surgery, University Hospital of Oulu, Oulu, Finland;10. Musculoskeletal Centre, Finnish Institute of Occupational Health, Oulu, Finland;11. Department of Physical and Rehabilitation Medicine, University of Oulu, Oulu, Finland;12. Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan |
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| Abstract: | Lumbar disc herniation (LDH) is one of the most common musculo‐skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA1217 (alias SKT, the human homolog of murine Skt Sickle tail]) is a good candidate for an LDH susceptibility gene because SKT is specifically expressed in nucleus pulposa of intervertebral discs (IVDs) in humans and mice, and SktGt mice, which are established through a large‐scale gene‐trap mutagenesis, exhibit progressive, postnatal onset abnormality of the IVDs. Here, we report the association of SKT with LDH. Using tag SNPs, we examined the association in two independent Japanese case‐control populations and found a significant association with SKT rs16924573 in the allele frequency model (p = 0.0015). The association was replicated in a Finnish case‐control population (p = 0.026). The combined p value of the two population by meta‐analysis is 0.00040 (OR, 1.34; 95% CI, 1.14–1.58). Our data indicate that SKT is involved in the etiology of LDH. |
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| Keywords: | lumbar disc herniation KIAA1217 SKT intervertebral disc meta‐analysis |
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