Functional Impact of Human Collagen α2(XI) Gene Polymorphism in Pathogenesis of Ossification of the Posterior Longitudinal Ligament of the Spine

Abstract

Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen ␣2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL.(1) In the present study, a strong allelic association with non-OPLL (p ‫؍‬ 0.0003) was observed with an intron 6 polymorphism [intron 6 (؊4A)], in which the intron 6 (؊4A) allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6 (؉28A)] was in linkage disequilibrium with the intron 6 (؊4A). The functional impact of the polymorphisms was analyzed by comparing the differences in messenger RNA

Ossification of the posterior longitudinal ligament: a review

“…Retaining exon 7 together with removal of exon 6 observed in intron 6(-4A) in the COL11A2 gene could play a protective role in the ectopic ossification process. 70 Maeda et al 71 reported a sex-specific association of the COL11A2 haplotype with OPLL in male patients. However, a recent study by Horikoshi et al 38 could not reproduce the association between this gene and OPLL.…”

The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1

“…Because genetic factors appear to play crucial roles in the etiology of OPLL, genetic screenings to identify susceptibility are important. To date, we have performed genetic linkage and linkage disequilibrium studies to identify the causalities of OPLL and have successfully identified collagen 11A2 (COL11A2) and collagen 6A1 (3)(4)(5)(6). We also demonstrated that an intron 6 (Ϫ4a) polymorphism of COL11A2 affects the splicing of exon 6 in ligament cells from OPLL patients (5).…”

“…To date, we have performed genetic linkage and linkage disequilibrium studies to identify the causalities of OPLL and have successfully identified collagen 11A2 (COL11A2) and collagen 6A1 (3)(4)(5)(6). We also demonstrated that an intron 6 (Ϫ4a) polymorphism of COL11A2 affects the splicing of exon 6 in ligament cells from OPLL patients (5). Although the identification of genetic factors of OPLL has important implications, the overall picture of the molecular pathogenesis is still unclear, mainly because a subtle biological effect of the variant is the only observation, and, therefore, the biological significance of the variant is still obscure.…”

HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort

“…This pattern was similar to that found by Lee et al 15 Polymorphisms in COL11A2 have been implicated in susceptibility to skeletal and cartilage disorders, and hearing loss. [27][28][29][30][31][32] HLA-DPB1 is an attractive candidate gene for RA within this region, as it has an important role in the immune system by presenting peptides to CD4 þ T cells. Furthermore, the other two genes encoding classical HLA class II molecules, HLA-DRB1 and HLA-DQA1, are established RA risk genes.…”