Human retinoic X receptor beta: Complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic hone formation in the ligament, OPLL is a very com mon disorder, in fact it constitutes the lending 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 chromosom e 6. As a candidate gene approach, retinoic X receptor beta (RXR beta), ass igned to chromosome 6p21.3 adjacent to HLA class III was analyzed for a pos sible causality. To start screening for the molecular variants of RXR beta in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXR beta and elucidated the genomic organization of the gene, The human RXR beta is composed of 10 exons spanning over 6.2 kb of gnomic D NA. Sequence analysis of the promoter region revealed a GC-rich sequence wi thout TATA motif, We have identified three distinct molecular variants, one was in exon 10 and two were in the intergenic region between RXR beta and collagen 11A2 (COL11A2). Two variants in the intergenic region, 3' end + 14 0 and 3' end + 561, exhibit statistically significant associations with OPL L in case-control study (p = 0.0028 for 3' end + 140 and p = 0.034 for 3' e nd + 561). These results indicate that the genetic causality of OPLL Lies w ithin or close to the RXR beta/COL11A2 locus.