title: Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine.
abstract: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord. Based on the fact that the nucleotide pyrophosphatase (Npps) gene is responsible for ectopic ossification in ttw, an OPLL model mouse, the possibility was explored whether the human NPPS gene is associated with susceptibility to and severity of OPLL. First, we screened for single-nucleotide polymorphisms (SNPs) in the human NPPS locus using selected 25 OPLL patients with young onset (< 35 years old) or severe ossification (> 10 ossified vertebrae), and identified three novel SNPs in the locus. A case-control association study between 180 OPLL patients and 265 non-OPLL controls showed that one of these SNPs, IVS15-14T --> C substitution, was more frequently observed in OPLL patients (p = 0.022), especially in those with severe ossification (p < 0.0001) and young onset (p = 0.002), than in controls. A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification. We conclude that the IVS15-14T --> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Institute of Medical Science, University of Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Koshizuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ogata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Mabuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Seichi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000818:Animals; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*
chemical_list: D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase