HIF-1α polymorphism in the susceptibility of cervical spondylotic myelopathy and its outcome after anterior cervical corpectomy and fusion treatment

Abstract

Background: To investigate the association between the single nucleotide polymorphism (SNP) of hypoxia-inducible factor1 α (HIF-1α) and the susceptibility to cervical spondylotic myelopathy (CSM) and its outcome after surgical treatment.

Method: A total of 230 CSM patients and 284 healthy controls were recruited. All patients received anterior cervical corpectomy and fusion (ACF) and were followed for 12 months. The genotypes for two HIF-1α variants (1772C>T and 1790G>A) were determined.

Results: In the present study, we found that the HIF-1α polymorphism at 1790G>A significantly affects the susceptibility to CSM and its clinical features, including severity and onset age. In addition, the 1790A>G polymorphism also determines the prognosis of CSM patients after ACF treatment. The GG genotype of 1790G>A polymorphism is associated with a higher risk to develop CSM, higher severity and earlier onset age. More importantly, we found that the 1790G>A polymorphism determines the clinical outcome in CSM patients who underwent ACF treatment.

Conclusion: Our findings suggest that the HIF-1α 1790G>A polymorphism is associated with the susceptibility to CSM and can be used as predictor for the clinical outcome in CSM patients receiving ACF treatment.

Figure 1. HIF-1α polymorphisms with the clinical features of CSM patients.

Figure 1 shows that the 1790G>A dramatically affects the severity (Figure 1A) and onset age (Figure 1B) of CSM patients. Patients with the 1790GG had a higher mJOA score (Figure 1A) and earlier on set age (Figure 1B) than those with 1790GA and 1790AA genotypes (†, P<0.001).

Figure 2. The protein expressions of HIF-1α, VEGF, VEGFR and a series of inflammatory factors based on HIF-1α polymorphisms.

Figure 2 shows that only the 1790A>G polymorphism significantly affects the expression level of HIF-1α, VEGF, VEGFR, IL1, IL6 and NF-kB protein expressions compared to 1970AA and 1970AG. The OPG and OPN levels were not changed when stratified by 1790A>G polymorphism (Figure 2). The 1772C>T genotype did not influence the above mentioned factors expression levels.