title: A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation.
abstract: Lumbar disc herniation (LDH), degeneration and herniation of the nucleus pulposus of the intervertebral disc (IVD) of the lumbar spine, is one of the most common musculoskeletal diseases. Its etiology and pathogenesis, however, remain unclear. Type XI collagen is important for cartilage collagen formation and for organization of the extracellular matrix. We identified an association between one of the type XI collagen genes, COL11A1, and LDH in Japanese populations. COL11A1, which encodes the alpha 1 chain of type XI collagen, was highly expressed in IVD, but its expression was decreased in the IVD of patients with LDH. The expression level was inversely correlated with the severity of disc degeneration. A single-nucleotide polymorphism (c.4603C-->T [rs1676486]) had the most significant association with LDH (P=3.3 x 10(-6)), and the transcript containing the disease-associated allele was decreased because of its decreased stability. These observations indicate that type XI collagen is critical for IVD metabolism and that its decrease is related to LDH.
authors.affiliation: Laboratory for Bone and Joint Diseases, School of Medicine, Keio University, Tokyo.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Mio
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hirose
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mikami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oya
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamata
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000235:genetics; D024161:Collagen Type XI / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007405:Intervertebral Disc Displacement / Q000235:genetics*; D007564:Japan; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014158:Transcription, Genetic
chemical_list: D024161:Collagen Type XI