COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament

Study Design. A case-control association study was conducted to investigate the genetic etiology for ossification of the ligamentum flavum (OLF) and ossification of the posterior longitudinal ligament of the spine (OPLL). Objective. To determine whether COL6A1 polymorphisms are associated with susceptibility to OLF and OPLL in Chinese Han population. Summary of Background Data. The COL6A1 has been identified as a susceptibility gene for OPLL in Japanese. The susceptibility gene for OPLL may be different among various populations, so we investigated whether COL6A1 polymorphisms are also associated with OPLL in Chinese Han population. OLF and OPLL are similar in epidemiology, etiology, and pathology, and common coexist. Hereditary factors may be implicated in OLF and COL6A1 may be a potential susceptibility gene for OLF, so we investigated the relations between COL6A1 polymorphisms and OLF. Methods. Four known single nucleotide polymorphisms (SNPs) of COL6A1 were genotyped among 338 Chinese Han subjects by high throughput GenomeLab SNPstream genotyping system. Allele frequency and genotype distribution of each polymorphism were compared using a contingency chi(2) test between 183 cases (90 OPLL, 61 OLF, and 32 OPLL coexisting with OLF) and 155 controls. Results. Among 4 studied SNPs, allele frequency of promoter (-572T) SNP demonstrated the most significant difference not only between OPLL cases and controls (P = 2.65E-4), but also between OLF cases and controls (P = 7.38E-4). Moreover, the overall frequency of haplotypes constructed from promoter (-572), intron 32 (-29), and intron 33 (-20) SNPs showed significant difference not only between the patients with OPLL and controls, but also between the patients with OLF and controls ( P = 5.86E-3, P = 1.5E-8, respectively). Conclusion. This is the first report on SNPs of COL6A1 in OLF that suggests polymorphisms may be a risk factor for OLF. Our findings indicate that COL6A1 may be a common susceptibility gene for OLF and OPLL in Chinese Han population.