Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine.

Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is the predominant myelopathy among Japanese, and is usually diagnosed by ectopic bone formation in the paravertebral ligament in Japanese and other Asians. To detect genetic determinants associated with OPLL, we performed an extensive nonparametric linkage study with 126 affected sib-pairs using markers for various candidate genes by distinct analyses, SIBPAL and GENEHUNTER. Eighty-eight candidate genes were selected by comparing the genes identified by complementary DNA (cDNA) microarray analysis of systematic gene expression profiles during osteoblastic differentiation of human mesenchymal stem cells with the genes known to be involved in bone metabolism. Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage (p = 0.016, nonparametric linkage [NPL] score = 1.83). Of 64 genes known to be associated with bone metabolism, 7 showed weak evidence of linkage by SIBPAL analysis (p < 0.05): cadherin 13 (CDH13), bone morphogenetic protein 4 (BMP4), proteoglycan 1 (PRG1), transforming growth factor beta 3 (TGFb3), osteopontin (OPN), parathyroid hormone receptor 1 (PTHR1), and insulin-like growth factor 1 (IGF1). Among these genes, BMP4 (NPL = 2.23), CDH13 (NPL = 2.00), TGFb3 (NPL = 1.30), OPN (NPL = 1.15), and PTHR1 (NPL = 1.00) showed evidence of linkage by GENEHUNTER. Only BMP4 reached criteria of suggestive evidence of linkage. Because this gene is a well-known factor in osteogenetic function, BMP4 should be screened in further study for the polymorphism responsible.

• Authors: Kozo Furushima, Kazuki Shimo-Onoda, Shingo Maeda, Takahiro Nobukuni, Katsunori Ikari, Hiroaki Koga, Setsuro Komiya, Toshiaki Nakajima, Seiko Harata, Ituro Inoue
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 17 Issue 1 Pg. 128-37 (Jan 2002) ISSN: 0884-0431 [Print] England
• PMID: 11771659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BMP4 protein, human
• Bmp4 protein, mouse
• Bmp4 protein, rat
• Bone Morphogenetic Protein 4
• Bone Morphogenetic Proteins
• Crystallins

Topics

• Animals
• Artificial Intelligence
• Base Sequence
• Bone Morphogenetic Protein 4
• Bone Morphogenetic Proteins (genetics)
• Case-Control Studies
• Crystallins (genetics)
• Disease Models, Animal
• Female
• Gene Expression Profiling
• Genetic Linkage
• Genetic Testing
• Humans
• Male
• Mice
• Microsatellite Repeats
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Ossification of Posterior Longitudinal Ligament (genetics)
• Rats