Gender-specific haplotype association of collagen alpha 2 (XI) gene in ossification of the posterior longitudinal ligament of the spine

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formati on in the paravertebral ligament. We have provided genetic evidence that th e collagen alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes suscepti bility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), iden tified in COL11A2 were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compare d in OPLL patients and non-OPLL controls. We report a gender-specific assoc iation of the COL11A2 haplotype with OPLL. The frequency of the most common ly observed haplotype was significantly higher in male patients (P = 0.0003 ) compared with controls, but not in female patients (P = 0.21). OPLL is pr edominantly observed in males, with a prevalence ratio of 2:1, and our gend er-specific associations indicate that genetic factors involving COL11A2 pl ay a specific role in the etiology of OPLL exclusively in males.