Repozitorij Medicinskog fakulteta Sveučilišta u Zagrebu

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

Kolundžić, Robert and Orlić, Dubravko and Trkulja, Vladimir and Pavelić, Krešimir and Gall Trošelj, Koraljka (2006) Single nucleotide polymorphisms in the interleukin-6 gene promoter, tumor necrosis factor-alpha gene promoter, and transforming growth factor-beta 1 gene signal sequence as predictors of time to onset of aseptic loosening after total hip arthroplasty: preliminary study. Journal of Orthopaedic Science, 11 (6). pp. 592-600. ISSN 0949-2658 (Print) 1436-2023 (Electronic)

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    English abstract

    BACKGROUND: Aseptic loosening resulting from inflammatory response to the implant wear debris is the major cause of late total hip arthroplasty (THA) failure. We examined single nucleotide polymorphisms in genes encoding for three involved cytokines - interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) - as potential predictors of time to onset of aseptic instability. - - - - - METHODS: A total of 41 patients/45 total hip endoprostheses (same type, same surgeon) were followed up for as long as 18 years. They were genotyped for the IL-6 promoter (-597G-->A) and (-572G-->C), TNF-alpha promoter (-308G-->A), and TGF-beta1 signal sequence ((29)T-->C) transitions. Cox regression was performed on the prosthesis survival. - - - - - RESULTS: Overall, 22 of 45 prostheses developed aseptic instability. Cumulative survivals at 10 and 15 years after THA were 95.6% and 66.6%, respectively. The 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. The hazard ratio (HR) for genotype T/T versus "C-allele carriage" at the TGF-beta1 site was 8.23 [95% confidence interval (CI) 1.45-46.8] (P = 0.017) or 5.70 (1.39-23.4) (P = 0.016) when the IL-6 promoter sites were considered as a "combination of genotypes (-597) | (-572)." The most prevalent combination of genotypes at IL-6 sites was G/A (-597) | C/C (-572). HR for this combination (versus other combinations) was 5.43 (1.73-17.0) (P = 0.004) when "TGF-beta1 ((29)T-->C)" was considered as a three-level factor (three possible genotypes), and 4.92 (1.71-14.1) (P = 0.003) when TGF-beta1 site was considered as a two-level factor (T/T and "C-allele carriage"). The HR for the "A-allele carriage" at TNF-alpha (-308G-->A) could not be determined (only two patients had the G/G genotype). - - - - - CONCLUSIONS: This preliminary study is the first to suggest that the TGF-beta1 signal sequence ((29)T-->C) and IL-6 promoter (-597G-->A) | (-572G-->C) transitions are predictive for the time to onset of aseptic instability after THA.

    Item Type: Article
    MeSH: Hip Prosthesis ; Polymorphism, Single Nucleotide ; Prosthesis Failure ; Interleukin-6 - genetics ; Transforming Growth Factor beta1 - genetics ; Tumor Necrosis Factor-alpha - genetics ; Adult ; Arthroplasty, Replacement, Hip ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Promoter Regions, Genetic ; Proportional Hazards Models
    Divisions: Katedra za farmakologiju
    Katedra za ortopediju
    Depositing User: Lea Škorić
    Status: Published
    Creators:
    CreatorsEmail
    Kolundžić, Robert
    Orlić, Dubravko
    Trkulja, Vladimir
    Pavelić, Krešimir
    Gall Trošelj, Koraljka
    Date: November 2006
    Date Deposited: 30 Jan 2007
    Last Modified: 23 Sep 2011 18:09
    Subjects: /
    Related URLs:
      URI: http://medlib.mef.hr/id/eprint/202

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