Genetic and immunological markers predict titanium implant failure: a retrospective study

This study evaluates diagnostic markers to predict titanium implant failure. Retrospectively, implant outcome was scored in 109 subjects who had undergone titanium implant surgery, ILIA - 889 C/T (rs1800587), IL1B + 3954 C/T (rs1143634), IL1RN + 2018 TIC (rs419598) and TNFA - 308 G/A (rs1800629) genotyping, in vitro IL-1 beta/TNF-alpha release assays and lymphocyte transformation tests during treatment. TNF-alpha and IL-1 beta release on titanium stimulation were significantly higher among patients with implant loss (TNF-a: 256.89 pg/ml vs. 81.4 pg/ml; p < 0.0001; IL-1 beta: 159.96 pg/ml vs. 54.01 pg/ml; p < 0.0001). The minor alleles of the studied polymorphisms showed increased prevalence in the implant failure group (IL1A: 61% vs. 42.6% in controls, IL1B: 53.7% vs. 39.7% in controls, TNFA: 46.3% vs. 30.9% in controls, IL1RN: 58.5% vs. 52.9% in controls). Increasing numbers of risk genotypes of the studied polymorphisms were associated with an increasing risk of implant loss, suggesting an additive effect. Multiple logistic regression analysis showed positive IL-1 beta/TNF-alpha release assay scores (p < 0.0001, OR = 12.01) and number of risk genotypes (p < 0.046, OR = 1.57-6.01) being significantly and independently associated with titanium implant failure. IL-1/IL1RN/TNFA genotyping and cytokine release assay scores provide prognostic markers for titanium implant outcome and may present new tools for individual risk assessment.