Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10(-11)]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10(-4)] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10(-5)]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

• Klíčová slova
• MUC2, MUC5B, association study, cytokines, idiopathic pulmonary fibrosis, network analysis, sequenom MassARRAY, single nucleotide polymorphism,
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• Czech normal population, MUC5B, association study, cytokines, idiopathic pulmonary fibrosis, sequenom MassARRAY, single nucleotide polymorphism, susceptibility,
• Publikační typ
• časopisecké články 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
• Názvy látek
• interleukin-1beta MeSH
• interleukin-6 MeSH
• TNF-alfa MeSH

AIM: To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations. METHODS: Twelve Finnish patients with autoimmune-type severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen I and Helicobacter pylori (H. pylori) antibodies. DNA was separated and the patients were genotyped for HLA-A, B, Cw, DRB1 and DQB1 antigens, and studied for single nucleotide polymorphisms for the following cytokines: interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon gamma, transforming growth factor beta, and tumor necrosis factor alpha. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations. RESULTS: All patients had pepsinogen I levels below normal (mean: 11 microg/L, range: < 5 to 25 microg/L). Three patients had elevated H. pylori IgG antibodies, while H. pylori serology was negative in the rest of the patients. AIG patients carried significantly more often HLA-DRB1*04 (58%) and DQB1*03 (83%) than the general Finnish population did (28% and 51%, respectively; P = 0.045 and 0.034 by the Fisher's exact test). No patient was positive for HLA-B8-DRB1*03, a well-established autoimmune marker. Neither cytokine polymorphisms nor KIR gene variation showed association with AIG. CONCLUSION: As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.

• MeSH
• autoimunitní nemoci etnologie   genetika   MeSH
• cytokiny genetika   MeSH
• dospělí MeSH
• draslíkové kanály dovnitř usměrňující genetika   MeSH
• gastritida etnologie   genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• HLA-DQ antigeny genetika   MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DR antigeny genetika   MeSH
• HLA-DRB1 řetězec MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Finsko MeSH
• Itálie MeSH
• Názvy látek
• cytokiny MeSH
• draslíkové kanály dovnitř usměrňující MeSH
• HLA-DQ antigeny MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQB1 antigen MeSH Prohlížeč
• HLA-DR antigeny MeSH
• HLA-DRB1 řetězec MeSH
• HLA-DRB1*04 antigen MeSH Prohlížeč
• membránové glykoproteiny MeSH

BACKGROUND: The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype. METHODS: We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model. RESULTS: Univariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019). CONCLUSION: Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.

• MeSH
• alely MeSH
• cytokiny genetika   MeSH
• dospělí MeSH
• genetické asociační studie * MeSH
• interleukin-2 genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu škodlivé účinky   MeSH
• odds ratio MeSH
• osteolýza etiologie   genetika   MeSH
• proporcionální rizikové modely MeSH
• receptory cytokinové genetika   MeSH
• rizikové faktory MeSH
• selhání protézy * MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH
• interleukin-2 MeSH
• interleukin-6 MeSH
• receptory cytokinové MeSH
• TNF-alfa MeSH

Recent study in a group of German patients with SSc has implicated the SNP in the MCP-1 gene (-2518 A to G) as a factor of susceptibility to SSc. Reflecting the need for replication of genetic association studies, we investigated if this SNP is associated with SSc in another Caucasian population. MCP-1 -2518 A/G genotypes were determined using PCR-SSP in 46 SSc patients and in 449 healthy subjects, all unrelated and of Slovak (Slavonic) origin. The distribution of MCP-1 -2518 A/G genotypes complied with the Hardy-Weinberg equilibrium both in patient and healthy control groups. There was no difference in MCP-1 -2518*G allele frequency between SSc patients and healthy subjects (patients: 0.23; controls: 0.24; P > .05). Furthermore, MCP-1 -2518 GG homozygotes were similarly represented among SSc patients and healthy subjects (P > .05). The association of MCP-1 -2518 A/G SNP with SSc observed originally in German population was not replicated in the Slovak population.

• MeSH
• chemokin CCL2 genetika   MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• studie případů a kontrol MeSH
• systémová sklerodermie genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CCL2 protein, human MeSH Prohlížeč
• chemokin CCL2 MeSH