The most common reasons for total joint arthroplasty (TJA) failure are aseptic loosening (AL) and prosthetic joint infection (PJI). There is a big clinical challenge to identify the patients with high risk of AL/PJI before the TJA surgery. Although there is evidence that genetic factors contribute to the individual susceptibility to AL/PJI, a predictive model for identification of patients with a high genetic risk of TJA failure has not been developed yet.

We aimed to develop a risk evaluation tool utilising the AL/PJI-associated polymorphisms for identification of patients with high genetic risk of TJA failure based on inflammation-gene polymorphism panel.

Based on allele and genotype frequencies of twenty-five single nucleotide polymorphisms (SNPs) in TNF, IL2, IL6, IL10, IL1b, IL-1Ra, MBL2, MMP1, FTO genes and those influencing the serum levels of biomarkers of TJA outcomes (IL6, CCL2/MCP-1, CRP, ESR) in peripheral blood obtained from patients with TJA (AL, n=110; PJI, n=93; no complications, n=123), we calculated a hazard ratio and a relative entropy of alleles and genotypes associated with AL and PJI and their combinations in patient subgroups.

We conducted a risk evaluation tool based on the presence of risk alleles and genotypes in TNF (rs361525, rs1800629), DARC (rs12075), MBL2 (rs11003125) and FTO (rs9939609, rs9930506) genes associated with implant failure (AL/PJI). Of these, FTO gene variations (rs9939609, rs9930506) were associated mainly with PJI (P=0.001, OR=2.04, 95%CI=1.132–2.603; P=0.011, OR=1.72, 95%CI=1.338–3.096) and DARC (rs12075) with AL (P=0.005, OR=1.79, 95%CI=1.193–2.696). This tool calculates a hazard ratio of a combination of SNPs associated with AL and PJI for identification of patients with high and low risk of AL/PJI TJA failure.

We proposed a risk evaluation tool for stratification of patients before the TJA surgery based on the genetic risk of AL/PJI development. The effect size for each genotype combination described in the study is small. Further multiparametric data analysis and studies on an extended patient cohort and other non-genetic and genetic parameters are ongoing. Grant support: AZV MZ CR VES16-131852A, VES15-27726A, IGA LF UP_2016_011.

Introduction: The development of periprosthetic osteolysis (OL) in total hip arthroplasty (THA) depends on activation of distinct pathways by wear particles eventually leading to predominance of osteoclasts over osteoblasts at the bone-implant interface. These processes are orchestrated by many cytokines and chemokines. However, interindividual variability in OL was observed even in cases of comparable wear rates and identical prosthesis. To explain it, we hypothesize genetic susceptibility to OL underlined by single nucleotide polymorphisms (SNP) for genes for key signal molecules.

Patients and Methods: In this case-control association study we investigated patients with severe OL around THA (n=116). The control group included patients with the same THA and mild OL (n=89). All were Caucasian, all had a single type of cementless THA implanted at a single institution. Healthy subjects without THA (n=150) served as a genetic background. Severity of OL was determined according to the Saleh’s classification. We used the candidate gene approach and overall, 22 cytokine/cytokine receptor SNPs were genotyped by polymerase chain reaction with sequence specific primers (PCR-SSP).

Results: The results showed an association of the TNF-238*A allele with severe OL (odds ratio, OR=6.59, p=0.005, population attributable risk percentage, PAR% = 5.2), higher risk of revision (OR=infinity, p=0.017) and poorer survival of THA (p=0.022). In addition, carriers of the IL-6-174*G allele were more frequent among the patients with severe OL (OR=2.51, p=0.007, PAR%=31.5). Finally, the genetic variant IL-2-330*G was associated with lower risk for THA revision (OR=0.44, p=0.02), protection from severe OL (OR=0.55, p=0.043) and longer survival of THA (p=0.018).

Conclusions: At least in a Czech population, genetic variants of the pro-inflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL and risk of premature THA failure. Conversely, SNP in the IL-2 gene may protect from development of severe OL and risk of early revision due to OL.