A FUNCTIONAL POLYMORPHISM IN COL11A1 IS ASSOCIATED WITH SUSCEPTIBILITY TO LUMBAR DISC HERNIATION : Spine Journal Meeting Abstracts

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00152232-200911001-00021AbstractSpine: Affiliated Society Meeting AbstractsSpine: Affiliated Society Meeting Abstracts© 2009 Lippincott Williams & Wilkins, Inc.November 2009 p A FUNCTIONAL POLYMORPHISM IN COL11A1 IS ASSOCIATED WITH SUSCEPTIBILITY TO LUMBAR DISC HERNIATION2009 Abstract SubmissionMio, Futoshi; Chiba, Kazuhiro; Kawaguchi, Yoshiharu; Mikami, Yasuo; Seki, Shoji; Mori, Masaki; Hirose, Yuichiro; Kubo, Toshikazu; Kimura, Tomoatsu; Toyama, Yoshiaki; Ikegawa, ShiroSubmitted Thu, 13 Nov 2008 23:42:20 -0500Presenter's Name Mio FutoshiAuthor for Correspondence Mio FutoshiAuthor's Address Shinanomachi 35 Shinjuku, Tokyo 160-8582 JapanAuthor's Phone +81-3-5363-3812Author's Fax +81-3-3353-6597Author's [email protected] Type OriginalPermission to Publish YesPresentation Type Paper_or_PosterCategory 4. Disc Degeneration/ArthritisIntroduction Lumbar disc herniation (LDH) affects the activities of daily living of patients. Etiology of LDH remains unknown. Through extensive case-control association studies of candidate genes encoding ECM proteins in intervertebral disc, we identified SNP in gene “COL11A1” that encodes alfa1 chain of collagen type XI that has a strong association with the occurrence of LDH.Methods This study was approved by ethical committees of all participating institutes. All subjects were Japanese. All LDH cases had unilateral pain with duration over 3 months. Their plain radiographs and MRI were found to have positive findings indicating disc herniation.Large case-control association studies of various SNPs in 823 cases of LDH and 841 healthy controls using candidate gene approach were conducted. SNPs were chosen from the International HapMap Project and JSNP databases. We identified additional sequence variations in COL11A1 by direct sequencing of 230-kb region of DNA from 24 cases.Results A SNP (c.4603C>T; rs1676486) in COL11A1 that is highly expressed in normal intervertebral disc showed significant association with occurrence of LDH (P =0.0000033). COL11A1 expression was decreased in intervertebral disc of LDH patients. We quantified the allelic difference by allele specific PCR and confirmed decreased expression of the susceptible allele (T) in vivo. To investigate cause of decreased expression, we examined stability of COL11A1 mRNA by northern blot analysis. Transcript containing T allele degraded faster than those with non-susceptible C allele.Discussion Unstable COL11A1 transcript degraded faster, possibly resulting in altered ECM function, and might have increased occurrence of LDH. Our results would lead to understanding of pathomechanism of LDH, which may ultimately lead to development of novel therapeutic strategies for LDH.<strong xmlns:mrws="http://webservices.ovid.com/mrws/1.0">A FUNCTIONAL POLYMORPHISM IN COL11A1 IS ASSOCIATED WITH SUSCEPTIBILITY TO LUMBAR DISC HERNIATION</strong>Mio Futoshi; Chiba, Kazuhiro; Kawaguchi, Yoshiharu; Mikami, Yasuo; Seki, Shoji; Mori, Masaki; Hirose, Yuichiro; Kubo, Toshikazu; Kimura, Tomoatsu; Toyama, Yoshiaki; Ikegawa, Shiro2009 Abstract Submission2009 Abstract Submission