BACKGROUND AND AIMS: Osteoprotegerin (OPG; official gene symbol: TNFRSF11B) is considered a negative regulator of bone resorption via inhibition of osteoclast differentiation. Further, OPG expression has been detected in Prosthetic Joint Infection (PJI) a serious complication limiting the overall outcome of total joint arthroplasty (TJA). As OPG may be a candidate molecule for PJI pathogenesis, we investigated whether genetic variation in the OPG promoter, namely the SNP at position -163 was associated with PJI. METHODS: OPG -163 T/C SNP (rs3102735) was genotyped by polymerase chain reaction with sequence specific primers (PCR-SSP) in 98 Czech patients with PJI and two Czech control groups: 1) aseptic TJA control [251 patients with TJA who did not develop PJI at least 6 yrs. after the surgery] and 2) population control (185 healthy control subjects without TJA). RESULTS: The distribution of OPG -163 SNP genotypes complied with the Hardy-Weinberg equilibrium in all three groups. The allele frequencies of OPG -163 SNP were similar in patients with PJI (minor allele frequency: 0.14), those with aseptic TJA (0.13) and population controls (0.14, P>0.05). Further, there was no significant difference in genotype or phenotype frequency (carriage rate) between patients with PJI and both control groups (P>0.05). CONCLUSIONS: In a Czech population, the OPG -163 T/C SNP has not been found to be associated with PJI.
- MeSH
- artroplastiky kloubů škodlivé účinky MeSH
- dospělí MeSH
- genotyp MeSH
- infekce spojené s protézou genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- osteoprotegerin genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVE AND DESIGN: Prosthetic joint infection (PJI) is a severe complication of total joint arthroplasty (TJA). We conducted a genetic association study that investigated whether selected coding variants of the genes for Toll-like receptors (TLR)2 and TLR4 may contribute to genetic susceptibility for PJI. SUBJECTS AND METHODS: In total, 350 patients with TJA (98 with PJI/252 without PJI), and 189 unrelated healthy Czech individuals without TJA were enrolled in our study. Three missense polymorphisms of the genes encoding for TLR2 (TLR2 R753Q, rs5743708) and TLR4 (TLR4 D299G, rs4986790 and T399I, rs4986791) were genotyped by "TaqMan" assay. RESULTS: The frequencies of less common variants for the investigated TLR2/TLR4 polymorphisms in healthy individuals were similar to those observed in other Caucasian populations. Importantly, the distribution of TLR2/TLR4 genotype alleles did not differ between the patients with PJI and the control groups of patients with nonseptic prostheses/healthy individuals. CONCLUSION: Our data suggest that structural genetic variants of the receptors TLR2 and TLR4 do not substantially affect the risk of prosthetic joint infection.
- MeSH
- artroplastika MeSH
- infekce spojené s protézou genetika MeSH
- infekce MeSH
- jednonukleotidový polymorfismus MeSH
- klouby chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protézy a implantáty škodlivé účinky MeSH
- senioři MeSH
- stafylokokové infekce genetika MeSH
- Staphylococcus MeSH
- toll-like receptor 2 genetika MeSH
- toll-like receptor 4 genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Prosthetic joint infection (PJI) is an important failure mechanism of total joint arthroplasty (TJA). Here we examine whether the particular genetic variants can lead to increased susceptibility to PJI development. RESULTS: We conducted a genetic-association study to determine whether PJI could be associated with functional cytokine gene polymorphisms (CGP) influencing on innate immunity response. A case-control design was utilized and previously published criteria for PJI were included to distinguish between cases and control subjects with/without TJA. Six single nucleotide polymorphisms (SNPs) located in the genes for interleukin-1beta (SNP: IL1B-511, +3962), tumour necrosis factor alpha (TNF-308, -238) and interleukin-6 (IL6-174, nt565) were genotyped in 303 Caucasian (Czech) patients with TJA (89 with PJI / 214 without PJI), and 168 unrelated healthy Czech individuals without TJA. The results showed that carriers of the less common IL1B-511*T allele were overrepresented in the group of TJA patients with PJI (69%) in comparison with those that did not develop PJI (51%, p = 0.006, p(corr) = 0.037) and with healthy controls (55%, p = 0.04, p(corr) = N.S.). There was no significant difference in the distribution of the remaining five investigated CGPs and their haplotypes between groups. CONCLUSION: A functional variant of the gene encoding for IL-1beta was preliminarily nominated as a genetic factor contributing to the susceptibility to PJI. Our results should be independently replicated; studies on the functional relevance of IL1B gene variants in PJI are also needed.
- MeSH
- artroplastika * MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- infekce spojené s protézou genetika MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutační analýza DNA MeSH
- polymorfismus genetický MeSH
- protézy kloubů škodlivé účinky MeSH
- studie případů a kontrol MeSH
- TNF-alfa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH