RUNX2 Polymorphisms Associated with OPLL and OLF in the Han Population

Background Runt-related transcription factor 2 (RUNX2), BMP-2, COL6A1, and VDR are four genes that may be related to ossification of the spinal ligament. However, their pathogenetic relevance remains unclear. Most cases of ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) have been reported in Asian populations, but the polymorphic loci in these genes may vary among people of different races. Purposes We identified (1) polymorphic loci in four genes (RUNX2, BMP-2, COL6A1, and VDR) in OPLL and OLF in Chinese Han patients and (2) identified loci related to these diseases. Methods We analyzed 19 single nucleotide polymorphisms (SNPs) in four candidate genes in 200 Han individuals (82 patients and 118 control subjects) by the Sequenom system. The genotype distribution and allele frequency of each SNP in the control and patient groups were compared. We then determined the relationships between the loci and the occurrence of OPLL and OLF. Results Genotyping showed RS1321075 and RS12333172 in RUNX2 differed between the patients and the control subjects. Both loci were located on chromosome 6 and exhibited linkage disequilibrium. One of the two blocks was a haplotype, thus suggesting a link between this block and increased incidence of OPLL and OLF. Conclusion Although the detailed mechanism of the SNP is unclear, our data suggest RUNX2 could be responsible for ectopic bone formation in the spinal ligament in the Chinese Han population. However, we found no obvious connection between polymorphic loci of COLA1, BMP-2, and VDR and the diseases. Clinical Relevance Molecular genetic studies have identified several candidate genes that may be responsible for increased susceptibility to the diseases. Information regarding SNPs among the certain candidate genes may improve understanding of the disease and assist in developing new diagnostic gene tools during early episodes of the disease.