OPN Polymorphism is Associated with the Susceptibility to Cervical Spondylotic Myelopathy and its Outcome After Anterior Cervical Corpectomy and Fusion

Abstract

Background: Osteopontin (OPN) is reportedly involved in bone desorption, formation and ectopic calcification. We sought to investigate the role of OPN gene polymorphism in the susceptibility to Cervical spondylotic myelopathy (CSM) and in predicting the outcome anterior cervical corpectomy and fusion (ACF). Methods: A total of 187 patients diagnosed with CSM and 233 sex and age matched healthy controls were enrolled in this study. All CSM patients received ACF and were followed up for 24 months. The polymorphisms of OPN gene at 3 loci, namely, -156 G>GG, -443 C>T and -66T>G were determined. Results: The -66T>G genotype was significantly different between CSM patients and controls. Compared to the -66TT carriers, the -66GG genotype carriers had a higher risk for developing CSM (adjusted Odd Ratio=2.58, adjusted P=0.001). In contrast, the genotype distributions of the -156G/GG and -443C/T loci were not significantly different between the CSM and control groups. OPN gene polymorphism did not determine the pre-operative severity of CSM patients, but the -66T>G genotype was significantly associated with the clinical outcome of CSM after ACF treatment. The -66T>G did not affect the serum OPN level, but affect the local expressions of OPN and a serious of key inflammatory factors in the intervertebral disc samples. Conclusion: Our study shows the OPN -66T>G genetic polymorphism contributes to patients' susceptibility to CSM and could be indicative of the outcome of ACF surgery.

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

“…Wu et al (2014) studied three SNPs of the osteopontin (OPN) gene [43]. Two showed no significant effect, but the G allele of the -66T>G SNP was associated with an odds ratio of 1.55 of clinical onset of DCM (p = 0.002).…”

“…Yu et al (2018) found the TT genotype of the 950T>C polymorphism in the OPG gene to be associated with higher mJOA scores and fewer ossified vertebrae (p < 0.05); the TT genotype appears to be protective [42]. Wu et al (2014) investigated four polymorphisms of the OPN gene in 187 CSM patients, finding no significant difference of all four polymorphisms on the mJOA score [43].…”

“…In the OPN gene, the GG genotype of the −66T>G SNP was found to be associated with worse response to surgical intervention, as assessed by mJOA score (OR 3.62, p = 0.007) [43]. Good surgical response was defined as >50% improvement in mJOA score.…”

“…One study used the SF-36 quality of life survey [53], three used the mJOA score [35,43,51] (a clinical score commonly used in DCM research [58][59][60][61]), while others used radiographic measures [19,23,24,26,27,41,44,51]. A similar situation is found within the literature while considering response to surgery, with one study using a cut-off for 'improvement' as +1 point on mJOA score [54], some using >50% increase in mJOA score [25,35,43], one using a t-test of % improvement on mJOA between homozygous groups [44], and one paper while using a radiographic definition of disease progression [41]. Such heterogeneity of outcome measures limits the degree to which the effects of genes on severity of DCM and response to surgery can be compared.…”

Osteopontin, Bone Morphogenetic Protein-4, and Vitamin D Receptor Gene Polymorphisms in the Susceptibility and Clinical Severity of Spinal Tuberculosis

“…OPN -443C/T single nucleotide polymorphism is associated with the development of arterial calcification and bone density [13]. In addition, the OPN -66T>G genetic polymorphism contributes to patients susceptibility to cervical spondylotic myelopathy and is an indicator of the outcome of anterior cervical corpectomy and fusion surgery [14]. Several studies reported the roles of OPN in tuberculosis infection.…”