engleski

Single nucleotide polymorphisms in the interleukin-6 gene promoter, tumor necrosis factor-α gene promoter, and transforming growth factor-β 1 gene signal sequence as predictors of time to onset of aseptic loosening after total hip arthroplasty: preliminary study

Background. Inflammatory response to implant wear debris, resulting in aseptic loosening, is the major late complication after total hip arthroplasty. Prosthetic materials, as well as demographic and biomechanical factors, explain only a minor part of its variable occurrence. The impact of single nucleotide polymorphisms (SNPs) in the promoter region of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF- alpha), along with the SNP at position 29 in the coding region of transforming growth factor beta 1 (TGF-beta1) were examined with respect to the timing of aseptic instability. Methods: Forty one patients with 45 total hip endoprosheses were genotyped for SNPs at nucleotides -597 (A-C) and -572 (G-C) in the IL-6 promoter, -308 (G-A) in the TNF-α promoter and 29 (T-C) in the TGF-beta 1 coding region. The impact of specific genotypes on the onset time of aseptic instability was analyzed in a Cox proportional hazard regression model. Results. The median follow-up was 15 years, with 22/45 prostheses developing aseptic instability. The estimated median prosthesis survival was 18 years. The presence of “ C allele” , i.e., TC or CC genotypes in the TGF- beta 1 coding region was associated with a reduced risk of aseptic instability (vs. the TT genotype): adjusted RR 0.146 (95% CI 0.026 to 0.807 ; p= 0.027) and 0.143 (95% CI 0.024 to 0.861 ; p= 0.034), respectively. The heterozygous genotype at position -597 in the IL-6 promoter (GA) was associated with an increased risk of aseptic instability when compared with GG genotype RR 4.066 (95% CI 1.072 to 15.427 ; p= 0.039). The SNP in the TNF-alpha promoter region was also an independent predictor of the prosthesis survival (chi2 9.497, p=0.009 in analysis of deviance) but RRs associated with the particular genotypes could not be estimated due to the low frequency of the GG genotype. Conclusion. The analyzed SNPs in the IL-6, TNF- α and TGF-beta1 were shown to influence the onset time of aseptic instability after total hip arthroplasty. Level of evidence: Prognostic study, level II-1: retrospective study.

gene polymorphism ; hip endoprosthesis ; stability

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