Abstract
BackgroundThe differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype.MethodsWe performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model.ResultsUnivariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019).ConclusionGenetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.
Highlights
The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis
Study design and statistical analysis This study investigated eventual associations between severity of acetabular osteolysis in THA and twenty-two single-nucleotide polymorphisms (SNPs) across eleven genes coding for proinflammatory/immunomodulatory cytokines and for two cytokine receptor genes, all located across ten chromosomes
Clinical outcome of patients with THA according to the severity of OL Patients with severe osteolysis had significantly lower Harris Hip Score at the last follow-up in comparison with those with mild osteolysis
Summary
The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. The concept of cytokines as initiators and perpetuators of particle disease is supported by reports on proinflammatory cytokine (IL-1, IL-6, TNF-α) up-regulation in macrophages and fibroblasts in response to wear particles [5,6]. These pleiotropic cytokines substantially promote the recruitment and maturation of osteoclast precursors at the bone-prosthesis interface [7]. Particle disease/osteolysis might be facilitated by down-regulation of immunomodulatory cytokines with anti-osteoclastogenic properties (e.g. IL-4, IL-10, IFN-γ) as has been already demonstrated in inflammatory joint conditions [8,9]
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