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Variation in the IL1B, TNF and IL6 genes and individual susceptibility to prosthetic joint infection.

Stahelova A, Mrazek F, Smizansky M, Petrek M, Gallo J - BMC Immunol. (2012)

Bottom Line: There was no significant difference in the distribution of the remaining five investigated CGPs and their haplotypes between groups.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Immunogenomics and Immunoproteomics, Faculty of Medicine and Dentistry, Palacky University Olomouc, IP Pavlova 6, Olomouc 77520, Czech Republic.

ABSTRACT

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.

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The proportion of the carriers of less commonIL1B-511*T allele in the study groups. TJA – Total Joint Arthroplasty; PJI – Prosthetic Joint Infection. The p values and odds ratio for comparisons between the groups are provided in the Table 2.
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Figure 2: The proportion of the carriers of less commonIL1B-511*T allele in the study groups. TJA – Total Joint Arthroplasty; PJI – Prosthetic Joint Infection. The p values and odds ratio for comparisons between the groups are provided in the Table 2.

Mentions: Overall distribution of genotypes for IL1B-511 polymorphism differed nominally between TJA patients with PJI versus those without PJI (p = 0.014, pcorr > 0.05, 2 degrees of freedom), particularly due to the overrepresentation of IL1B-511 CT heterozygotes and reciprocal decrease of CC homozygotes among PJI patients. Importantly, the proportion of carriers of the less common IL1B-511*T allele was significantly higher in PJI patients (69%) than in those that did not develop PJI (51%, p = 0.006, pcorr = 0.037; odds ratio = 2.06, 95%CI: 1.22-3.47) or healthy controls (55%, p = 0.04, pcorr > 0.05; odds ratio = 1.76, 95%CI: 1.02-3.02), (Figure 2). Similarly, the allelic frequency of IL1B-511*T tended to be higher in the group of PJI patients by comparison to those with “aseptic” TJA (p = 0.052). The alleles and genotypes of the other five investigated cytokine gene polymorphisms were similarly distributed (p > 0.05) in all three groups (Table 2).The frequencies of two-locus haplotypes for each investigated cytokine gene estimated by expectation–maximisation algorithm are listed in Table 3. Consistent with the previous reports we detected strong LD between the alleles at two IL6 SNP loci (IL6-174 / nt565, p < 0.00001 for all groups). The results from a single locus analysis in IL1B gene were reflected also in a haplotype level: The IL1B −511/ +3962 TC haplotype tended to be more frequent in PJI patients by comparison to those without infection after TJA. Nevertheless, overall haplotype distribution did not significantly differ between the PJI patients and those that did not develop PJI for any of investigated IL1B, TNF and IL6 genes.


Variation in the IL1B, TNF and IL6 genes and individual susceptibility to prosthetic joint infection.

Stahelova A, Mrazek F, Smizansky M, Petrek M, Gallo J - BMC Immunol. (2012)

The proportion of the carriers of less commonIL1B-511*T allele in the study groups. TJA – Total Joint Arthroplasty; PJI – Prosthetic Joint Infection. The p values and odds ratio for comparisons between the groups are provided in the Table 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475038&req=5

Figure 2: The proportion of the carriers of less commonIL1B-511*T allele in the study groups. TJA – Total Joint Arthroplasty; PJI – Prosthetic Joint Infection. The p values and odds ratio for comparisons between the groups are provided in the Table 2.
Mentions: Overall distribution of genotypes for IL1B-511 polymorphism differed nominally between TJA patients with PJI versus those without PJI (p = 0.014, pcorr > 0.05, 2 degrees of freedom), particularly due to the overrepresentation of IL1B-511 CT heterozygotes and reciprocal decrease of CC homozygotes among PJI patients. Importantly, the proportion of carriers of the less common IL1B-511*T allele was significantly higher in PJI patients (69%) than in those that did not develop PJI (51%, p = 0.006, pcorr = 0.037; odds ratio = 2.06, 95%CI: 1.22-3.47) or healthy controls (55%, p = 0.04, pcorr > 0.05; odds ratio = 1.76, 95%CI: 1.02-3.02), (Figure 2). Similarly, the allelic frequency of IL1B-511*T tended to be higher in the group of PJI patients by comparison to those with “aseptic” TJA (p = 0.052). The alleles and genotypes of the other five investigated cytokine gene polymorphisms were similarly distributed (p > 0.05) in all three groups (Table 2).The frequencies of two-locus haplotypes for each investigated cytokine gene estimated by expectation–maximisation algorithm are listed in Table 3. Consistent with the previous reports we detected strong LD between the alleles at two IL6 SNP loci (IL6-174 / nt565, p < 0.00001 for all groups). The results from a single locus analysis in IL1B gene were reflected also in a haplotype level: The IL1B −511/ +3962 TC haplotype tended to be more frequent in PJI patients by comparison to those without infection after TJA. Nevertheless, overall haplotype distribution did not significantly differ between the PJI patients and those that did not develop PJI for any of investigated IL1B, TNF and IL6 genes.

Bottom Line: There was no significant difference in the distribution of the remaining five investigated CGPs and their haplotypes between groups.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Immunogenomics and Immunoproteomics, Faculty of Medicine and Dentistry, Palacky University Olomouc, IP Pavlova 6, Olomouc 77520, Czech Republic.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus