2000 Fiscal Year Final Research Report Summary
Genetic studies of ossification of the posterior longitudinal ligament of the spine
| Project/Area Number |
10470301
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo (2000)
Gunma University (1998-1999) |
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Principal Investigator |
INOUE Ituro Institute of Nedical Science, The University of Tokyo, Visiting Associate Professor, 医科学研究所, 客員助教授 (00192500)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Jun Gunma University, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (40270855)
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| Project Period (FY) |
1998 – 2000
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| Keywords | OPLL / ectopic bone formation / linkage study / association study / susceptibility / haplotype analysis / cDNA microarray |
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| Research Abstract |
Ossification of the posterior longitudinal ligament of the spine(OPLL)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.A strong allelic association with non-OPLL(P=0.0003)was observed with an intron 6 polymorphism(Intron 6(-4A)), where the intron 6(-4A)allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, five distinct SNPs, identified in COL11A2, were combined to construct possible haplotypes by use of a maximum likelihood program. Estimated haplotype frequency was compared between OPLL patients and non-OPLL controls and gender-specific association of COL11A2 haplotype with OPLL was observed. The most commonly observed haplotype was significantly increased in male patients(p=0.0003)but not in female patients(p=0.21). OPLL is a complex disease, and several genetic factors other COL11A2 are probably involved in the etiology, so the more extensive candidate gene approach was performed. We selected a total of 88 candidate genes based on two separate investigations. 24 genes differentially regulated during osteoblastic differentiation were selected by cDNA microarray analysis, and subjected to linkage analysis. We also selected 64 candidate genes that are possibly involved in bone metabolism or related conditions. Microsatellite markers, locating close to or within the candidate genes were obtained in the latest online information. With these markers we performed non-parametric linkage study with 126 OPLL sib-pairs to identify genetic loci responsible in OPLL.
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[Publications] Maeda, S., Ishidou, Y., Koga, H., Taketomi, E., Ikari, K., Komiya, S., Takeda, J., Sakou, T., Inoue, I.: "Functional impact of human collagen α 2(XI)gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine."J.Bone.Miner.Res.. (In press). (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yabe, I., Sasaki, H., Yamashita, I., Tashiro, K., Tatei, A., Suzuki, Y., Kida, H., Takiyama, Y., Nashizawa, M., Hokezu, Y., Nagamatsu, K., Oda, T., Ohnishi, A., Inoue, I., Hata, A.: "Predisposing chromosome of spinocerebellar ataxia type 6 6(SCA6)in Japanese."J.Med.Genet.. (In press). (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishigori, H., Tomura, H., Kanamori, M., Yamada, S., Kikuchi, N., Sho, K., Tonooka, N., Onigata, K., Inoue, I., Kojima, I., Yamagata, K.Yang, Q., Matsuzawa, Y., Kohama, T., Miki, T., Seino, S., Kim, M., Choi, H., Moore, D., Takeda, J.: "Mutations in the small heterodimer partner gene are associated with mild obesity in Japan."Proc.Natl.Acad.Sci.USA. 98. 575-580 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Maeda, S., Koga, H., Matsunaga, S., Numasawa, T., Takeda, J., Harata, S., Sakou, T., Inoue, I.: "Gender-specific haplotype association of collagen α2(XI)gene in ossification of the posterior longitudinal ligament of the spine."J.Hum.Genet.. 46. 1-4 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., Takeda, J.: "Molecular cloning of a novel brain-type Na^+-dependent inorganic phosphate cotransporter."J.Neurochem.. 74. 2622-2625 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada, S., Zhu, O., Aihara, Y., Onda, H., Zhang, Z., Yu, L., Jin, L., Si, YJ., Nishigoli, H, Tomura, H., Inoue, I., Morikawa, A., Yamagata, K., Hanafusa, T., Matsuzawa, Y., Takeda, J.: "Cloning of cDNA and the gene encoding human hepatocyte nuclear factor(HNF)-3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young."Diabetologia. 43. 121-124 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakajima, T., Tong, C., Rohrwasser, A., Bloem, LJ., Pratt, JH., Inoue, I., Lalouel, J-M.: "Functional analysis of a mutation occurring between the two in-frame AUG codons of human angiotensinogen."J.Biol.Chem.. 274. 35749-35755 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Onda, H., Kasuya, H., Takakura, K., Hori, T., Imaizumi, T., Takeuchi, T., Inoue, I., Takeda, J.: "Identification of genes differentially expression canine vasospastic cerebral arteries after subarachnoid hemorrhage."J.Cereb.Blood Flow Metab.. 19. 1279-1288 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Tomura, H., Nishigori, H., Sho, K., Yamagata, K., Inoue, I., Takeda, J.: "Loss-of-function and dominant-negative mechanisms associated with hepatocyte nuclear factor-1β mutations in familial type 2 diabetes mellitus."J.Biol.Chem.. 274. 12975-12978 (1999)
Description
「研究成果報告書概要(欧文)」より
