A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation.
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.
Mio
Futoshi
F
Laboratory for Bone and Joint Diseases, School of Medicine, Keio University, Tokyo.
Chiba
Kazuhiro
K
Hirose
Yuichiro
Y
Kawaguchi
Yoshiharu
Y
Mikami
Yasuo
Y
Oya
Takeshi
T
Mori
Masaki
M
Kamata
Michihiro
M
Matsumoto
Morio
M
Ozaki
Kouichi
K
Tanaka
Toshihiro
T
Takahashi
Atsushi
A
Kubo
Toshikazu
T
Kimura
Tomoatsu
T
Toyama
Yoshiaki
Y
Ikegawa
Shiro
S
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
D024161:Collagen Type XI