Hypothesis and objective

1. Tab 1. Characteristics of the patients with THA stratified according to the need for reoperation and OL severity Tab 2. Investigated SNPs and their alleles Wear Particles Genetic Factors Inflammation Bone Turnover Severe and mild OL according to Saleh et al. classification (J Bone Joint Surg Am, 83: 1040, 2001). Periprosthetic Osteolysis Premature THA Failure Fig 1. The frequency of less common alleles for six investigated SNPs in the patients with THA compared to control Czech population. Fig 2. Proportion of CXCL1 rs4074 AA genotype inthe patients with total hip athroplasty (THA) failure compared to those in the patients with functional primary THA Fig 2. Proportion of CXCL1 rs4074 AA genotype inthe patients with total hip athroplasty (THA) failure compared to those in the patients with functional primary THA the patients with THA versuscontrol Czech populationp > 0.05 (for all SNPs) THA failure versus functional primary THA p = 0.02 Fig 3. The frequencies of less common alleles for six investigated SNPs in the patients with revised THAcompared to those with functional primary THA. revisedTHA versus functional primary THA: p > 0.05 POLYMORPHISMS OF SELECTED CHEMOKINE AND CYTOKINE GENES AND RISK FOR FAILURE IN TOTAL HIP ARTHROPLASTYZ. Navratilova1, J. Gallo2, F. Mrazek1, R. Fillerova1, M. Petrek11 Laboratory of Immunogenomics and Proteomics, Dept. of Immunology2 Dept. of OrthopaedicsPalacky University and University Hospital Olomouc, Czech Republic Background Methods • Subjects • 205 unrelated Czech patients with cementless type THA - stratified according to: • 1) THA failure (reoperation) and 2) severity of OL.Table 1. • Genotyping • Genotyping technique: • Polymerase Chain Reaction with Sequence Specific Primers (PCR-SSP). Table 2. • 3.Statistics • Conformity of the distribution of genotypes to the Hardy-Weinberg equilibrium: χ2 goodness-of-fit test • Differences between allelic, genotype and phenotype („carriage rate“) frequencies: χ2 test. Periprosthetic osteolysis Periprosthetic osteolysis (OL) is major complication of the total hip athroplasty (THA) which can result in aseptic loosening and revision surgery. OL is considered as complex inflammatory response to wear particles liberated from the prosthetic surfaces. Recent findings support concept of genetic component of OL and aseptic loosening. Selection of candidate genes Cytokines and chemokines are though to be plausible candidates for implication in the pathogenesis of OL and aseptic loosening. Here we selected genes encoding six molecules involved in two (cytokine and chemokine) signalling pathways: 1) IL-17A, IL-17F and IL-23R are important regulators of immune response and may be associated with bone turnover 2) CXCL1, CXCL5 and their receptor CXCR2 promote accumulation of immune cells (namely neutrophils) in site of inflammation Hypothesis and objective Results Genotypes of all six investigated SNPs were distributed in compliance with the Hardy-Weinberg equilibrium. The distribution of alleles among the patients with THA corresponded to the frequencies observed in Czech healthy control population and other Caucasians (Figure 1). Out of investigated variants, CXCL1 rs4074 AA genotype was more frequent in the patients with functional primary prosthesis compared to those with revised THA (p = 0.02, Figure 2). The frequency of AA genotype in whole group of the patients with THA was same as that in Czech population (0.12). No further difference in the distribution of tested SNPs was observed between revised and unrevised THA patients (p > 0.05, Figure 3). None of the explored cytokine / chemokine SNPs was associated with the severity of OL (p > 0.05). The aim of the present study was to investigate possible association of single nucleotide polymorphisms (SNPs) within the genes encoding for CXCL1, CXCL5, CXCR2, IL-17A, IL-17F and IL-23R with severity of OL and THA failure (revision). Conclusions In this pilot study, less common AA genotype of CXCL1 rs4074 SNP appeared as a marker associated with the protection from total hip arthroplasty failure (revision). Our preliminary findings should be replicated in larger THA cohorts, optimally including more detailed and functional analysis of the CXCL1 gene variability. Studies of CXCL1 role in OL and aseptic loosening of THA are desirable as well. Conclusions Grant support: GACR 310/09/P377, IGA NS 10260 and MSM6198959223.