title: A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.
abstract: Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Horikoshi
authors.forename: Koichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Kanji
authors.initials: K
authors.lastname: Mori
authors.forename: Yu
authors.initials: Y
authors.lastname: Koshizuka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirabayashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Sugimori
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
authors.forename: Itsuro
authors.initials: I
authors.lastname: Inoue
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide