title: Association study of COL9A2 with lumbar disc disease in the Japanese population.
abstract: Lumbar disc disease (LDD) is a common musculo-skeletal disease with strong genetic determinants. In a Finnish population, a single nucleotide polymorphism (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes the alpha2 (IX) chain of type IX collagen, has been reported to associate with LDD. However, replication studies in different populations have produced controversial results. To further investigate the association of COL9A2 with LDD in Japanese, we examined SNPs in COL9A2, including Trp2, in 470 LDD patients (mean age 35) along with 658 controls (mean age 48). We identified a total of 43 sequence variations in COL9A2. Nine SNPs, including Trp2, were selected and genotyped. After Bonferroni's correction, none of these SNPs showed association. Unlike observations in the Finnish population, Trp2 was common in Japanese, and no association with LDD was apparent. However, we did see association of a COL9A2 specific haplotype with LDD (P=0.025; permutation test); this association is more significant in patients with severe lumbar disc degeneration (P=0.011). Thus, the association of Trp2 with LDD was not replicated, but COL9A2 susceptibility allele(s) other than Trp2 may be present in Japanese LDD.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Seki
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Mio
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mikami
authors.affiliation: Laboratory for Medical Informatics, SNP Research Center, RIKEN, Yokohama, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. sikegawa@ims.u-tokyo.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D024081:Collagen Type IX / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007403:Intervertebral Disc; D008159:Lumbar Vertebrae; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013122:Spinal Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014364:Tryptophan / Q000235:genetics
chemical_list: C120282:COL9A2 protein, human; D024081:Collagen Type IX; D014364:Tryptophan