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 (OSL).The polymorphic loci within these genes may vary among people of different races.Purposes The purpose of this study is to identify polymorphic loci within four genes including RUNX2, BMP-2, COL6A 1, and VDR in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) in Han Chinese patients, and to identify 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 pathologic groups were compared.We used statistical analyses to determine the relationships between the loci and the occurrence of OPLL and OLF.Results Genotyping showed RS 1321075 and RS 12333172 within RUNX2 were different between the patients and the control subjects.Both loci were on chromosome 6 and exhibited linkage disequilibrium.One of the two blocks was a haplotype suggesting a link between this block and increased incidence of OPLL/OLF.Conclusion SNP variation in RUNX2 might be the cause of OSL in the Chinese Han population, but 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 for susceptibility to the diseases.Information about SNPs among the certain candidate genes mayhelp us to better understand the disease and develop new diagnostic gene tools in early episode of the diseases.