engleski

Single nucleotide polymorphisms in IL-6, TNF-alfa1 and TGF-beta1 genes as predictors of time to onset of aseptic loosening after total hip arthroplasty

BACKGROUND. Aseptic loosening resulting from inflammatory response to the implant wear debris is the major cause of the late total hip arthroplasty (THA) failure. We examined single nucleotide polymorphisms in genes encoding for three involved cytokines - IL-6, TNF-alfa1 and TGF-beta1 - as potential predictors of time to onset of aseptic instability. METHODS. Forty one patients/45 total hip endoprostheses (same type, same surgeon) were followed-up for up to 18 years. They were genotyped for the IL-6 promoter (-597GA) and (-572GC), TNF-a promoter (-308GA) and TGF-beta1 signal sequence (29TC) transitions. Cox regression was performed on the prosthesis survival. RESULTS. Overall, 22/45 prostheses developed aseptic instability. Cumulative survival at 10 and 15 years after THA was 95.6% and 66.6%, respectively. Effect of a particular polymorphic site was estimated with adjustment for sex, age at THA, reason for THA and the effects of other analyzed sites. Hazard ratio (HR) for genotype T/T vs. “ C-allele carriage” at TGF-beta1 site was 8.23 (95% confidence interval 1.45 to 46.8), p=0.017 ; or 5.70 (1.39 to 23.4), p=0.016 when the IL-6 promoter sites were considered as a “ combination of genotypes (-597) and (-572)” . The most prevalent combination of genotypes at IL-6 sites was G/A (-597) and C/C (-572). HR for this combination (vs. other combinations) was 5.43 (1.73 to 17.0), p=0.004 when “ TGF-beta1 (29TC)” was considered as a 3-level factor (3 possible genotypes), and 4.92 (1.71 to 14.1), p=0.003, when TGF-beta1 site was considered as a 2-level factor (T/T and “ C-allele carriage” ). HR for the “ A-allele carriage” at TNF-a (-308GA) could not be determined (only 2 patients had the G/G genotype). CONCLUSION. This preliminary study is the first to suggest TGF-beta1 signal sequence (29TC) and IL-6 promoter (-597GA) and (-572GC) transitions as predictive for time to onset of aseptic instability after THA.

aseptic loosening; hip arthroplasty; single nucleotide polymorphisms

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