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Nucleotide Pyrophosphatase Gene Polymorphism Associated With Ossification of the Posterior Longitudinal Ligament of the Spine
Author(s) -
Koshizuka Yu,
Kawaguchi Hiroshi,
Ogata Naoshi,
Ikeda Toshiyuki,
Mabuchi Akihiko,
Seichi Atsushi,
Nakamura Yusuke,
Nakamura Kozo,
Ikegawa Shiro
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.1.138
Subject(s) - ossification , single nucleotide polymorphism , medicine , posterior longitudinal ligament , endocrinology , anatomy , gene , genetics , biology , genotype
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.