Association of Bone Metabolism Regulatory Factor Gene Polymorphisms With Susceptibility to Ossification of the Posterior Longitudinal Ligament of the Spine and Its Severity

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Abstract
A case–control association study and a stratified study investigating the genetic etiology for ossification of the posterior longitudinal ligament of the spine. To determine the association of restriction fragment length polymorphisms of estrogen receptor, vitamin D receptor, parathyroid hormone, and interleukin-1α and -1β with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity. Contribution of genetic backgrounds to the etiology for ossification of the posterior longitudinal ligament of the spine has been suggested by epidemiologic studies. Genomic deoxyribonucleic acid samples obtained from 120 patients (77 men and 43 women) with ossification of the posterior longitudinal ligament of the spine and 306 control subjects without the disorder (166 men and 140 women) were amplified by polymerase chain reaction, and polymorphism genotypes were determined by restriction endonuclease digestion. The distribution of genotypes was compared between patients with the disorder and control subjects. In addition, the severity of ossification was determined by the number of ossified vertebrae in patients with the disorder, and associations of the severity with age, gender, and genotypes were examined. Estrogen receptor (P = 0.007) and interleukin-1β (P = 0.001) polymorphisms exhibited different distributions between patients with ossification of the posterior longitudinal ligament of the spine and control subjects in women, but not in men. In patients with the disorder, the severity of ossification was negatively correlated with age in women (P = 0.013), but not in men. Estrogen receptor polymorphism was associated with the severity only in women (P = 0.001). The contribution of genetic backgrounds is likely to be stronger in women than in men with ossification of the posterior longitudinal ligament of the spine. Estrogen receptor polymorphism was associated with both initiation and promotion of the disorder, but interleukin-1β polymorphism was associated only with its initiation in women.