Premium
Human Retinoic X Receptor β: Complete Genomic Sequence and Mutation Search for Ossification of Posterior Longitudinal Ligament of the Spine
Author(s) -
Numasawa Takuya,
Koga Hiroaki,
Ueyama Kazumasa,
Maeda Shingo,
Sakou Takashi,
Harata Seiko,
Leppert Mark,
Inoue Ituro
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.4.500
Subject(s) - genetics , biology , locus (genetics) , exon , gene
Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the ligament. OPLL is a very common disorder, in fact it constitutes the leading cause of myelopathy among Japanese. In the previous report, we provided the genetic linkage evidence that the genetic susceptibility of OPLL mapped to HLA complex of chromosome 6. As a candidate gene approach, retinoic X receptor β ( RXR β), assigned to chromosome 6p21.3 adjacent to HLA class II, was analyzed for a possible causality. To start screening for the molecular variants of RXR β in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXR β and elucidated the genomic organization of the gene. The human RXR β is composed of 10 exons spanning over 6.2 kb of genomic DNA. Sequence analysis of the promoter region revealed a GC‐rich sequence without TATA motif. We have identified three distinct molecular variants, one was in exon 10 and two were in the intergenic region between RXR β and collagen 11A2 ( COL11A2 ). Two variants in the intergenic region, 3′ end + 140 and 3′ end + 561, exhibit statistically significant associations with OPLL in case‐control study ( p = 0.0028 for 3′ end + 140 and p = 0.034 for 3′ end + 561). These results indicate that the genetic causality of OPLL lies within or close to the RXR β/ COL11A2 locus.