Functional Impact of Human Collagen α2(XI) Gene Polymorphism in Pathogenesis of Ossification of the Posterior Longitudinal Ligament of the Spine
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- Shingo Maeda
- Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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- Yasuhiro Ishidou
- Department of Orthopedic Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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- Hiroaki Koga
- Department of Orthopedic Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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- Eiji Taketomi
- Department of Orthopedic Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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- Katsunori Ikari
- Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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- Setsuro Komiya
- Department of Orthopedic Surgery, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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- Jun Takeda
- Laboratory of Molecular Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
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- Takashi Sakou
- Sakou Clinic, Kagoshima, Kagoshima, Japan
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- Ituro Inoue
- Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
抄録
<jats:title>Abstract</jats:title> <jats:p>Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen α2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL.(1) In the present study, a strong allelic association with non-OPLL (p = 0.0003) was observed with an intron 6 polymorphism [intron 6 (−4A)], in which the intron 6 (−4A) allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6 (+28A)] was in linkage disequilibrium with the intron 6 (−4A). The functional impact of the polymorphisms was analyzed by comparing the differences in messenger RNA (mRNA) splicing by reverse-transcription polymerase chain reaction (RT-PCR) analysis in cultured cells from the interspinous ligament and an in vitro exon trapping study. The intron 6 (−4A) allele resulted in skipping exon 6 and retaining exon 7, while the exon 6 (+28A) allele was not associated with alteration in mRNA splicing. Similar mRNA species were observed in undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal ligament of non-OPLL subjects. The region containing exons 6-8 is an acidic subdomain presumably exposed to the surface that could interact with molecules of the extracellular matrix. Accordingly, retaining exon 7 together with removal of exon 6 observed in intron 6 (−4A) could play a protective role in the ectopic ossification process because the same pattern was observed in undifferentiated Ob cells and nonossified posterior longitudinal ligament cells.</jats:p>
収録刊行物
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- Journal of Bone and Mineral Research
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Journal of Bone and Mineral Research 16 (5), 948-957, 2001-05-01
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1363388845221485568
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- NII論文ID
- 30021655660
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- ISSN
- 15234681
- 08840431
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