SINGLE NUCLEOTIDE POLYMORPHISMS IN GENES FOR IL-2, IL-6 AND TNF-α INFLUENCE ON OSTEOLYSIS AND SURVIVAL OF TOTAL HIP ARTHROPLASTY

Abstract

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.