Polymorphism of IL-1[beta] rs16944 Associated with Serum Levels of IL-1[beta] and Subsequent Stimulation of Extracellular Matrix Degradation Affects Intervertebral Disk Degeneration Susceptibility

Purpose: To investigate the association of polymorphism of IL-1[beta] rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1[beta] for IDD. Patients and Methods: A total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age ([+ or -] 3 years). The polymorphisms of IL-1[beta] rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1[beta], MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student t-test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided P TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1[beta] levels in predicting IDD was 0.788 (SE: 0.023, P=0.001, 95% CI: 0.742-0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%. Conclusion: Polymorphism of IL-1[beta] rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1[beta] and subsequent stimulation of ECM degradation. IL-1[beta] levels could be applied in predicting IDD. Keywords: intervertebral disk degeneration, single-nucleotide polymorphisms, IL-1[beta], susceptibility, predictive value