Association between common polymorphisms in IL-1 and TNFα and risk of peri-implant disease: A meta-analysis

Background Pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) play important roles in host immune response and bone metabolism during dental implant osseointegration. Whether the functional polymorphisms in IL-1 alpha, IL-1 beta and TNF alpha were associated with peri-implant disease was unclear, and we performed the present meta-analysis for this purpose. Methods Eligible studies investigating IL-1 alpha C-889T, IL-1 beta C+3954T and C-511T, TNF alpha G-308A, composite genotype of IL-1 alpha C-889T and IL-1 beta C+3954T for association with peri-implant disease, including peri-implantitis (PI), marginal bone loss (MBL) and implant failure/loss (IF/IL), were searched on several literature databases prior to April 30, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for each polymorphism in different genetic models and for composite genotype comparing carriers to non-carriers. Results Twenty-seven studies (1324 cases with peri-implant disease and 1808 controls with healthy implants) were included. There was significant correlation between IL-1 alpha C-889T and peri-implant disease in all genetic models. IL-1 beta C+3954T was associated with peri-implant disease risk in allelic (OR = 1.66, 95%CI 1.17-2.35, p = 0.004) and dominant model (OR = 1.74, 95%CI 1.19-2.53, p = 0.004), and in subgroups of Asians, Caucasians, non-smokers, IF/IL and PI. TT genotype of IL-1 beta C-511T increased the risk of peri-implant disease (OR = 1.68, 95%CI 1.15-2.43, p = 0.007) and MBL (OR = 4.33, 95%CI 1.72-10.9, p = 0.002) compared to CC+CT genotypes. We did not observed a significant association between TNF alpha G-308A and peri-implant diseases in overall or subgroups analysis. Carriers of positive composite genotype of IL-1 alpha C-889T and IL-1 beta C+3954T had 1.95-fold (95%CI 1.35-2.80, p<0.001) risk of peri-implant disease and 1.76-fold (95%CI 1.05-2.95, p = 0.032) risk of IF/IL than non-carriers. Conclusion Functional polymorphisms of IL-1 alpha (C-889T), IL-1 beta (C+3954T, C-511T) and composite genotype of IL-1 can be used as predictive markers for peri-implant disease, whereas TNF alpha G-308A polymorphism was not associated with peri-implant disease.