Dataset Information

Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1? Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1?-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1?, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients' overall survival was analyzed with the Kaplan-Meier method with the log-rank test. Serum IL-1? concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1? compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

SUBMITTER: Ozretic P

PROVIDER: S-EPMC6826440 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of <i>NLRP1</i> Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

Ozretić Petar P da Silva Filho Miguel Inacio MI Catalano Calogerina C Sokolović Irena I Vukić-Dugac Andrea A Šutić Maja M Kurtović Matea M Bubanović Gordana G Popović-Grle Sanja S Skrinjarić-Cincar Sanda S Vugrek Oliver O Jukić Irena I Rumora Lada L Bosnar Martina M Samaržija Miroslav M Bals Robert R Jakopović Marko M Försti Asta A Knežević Jelena J

Genes 20191009 10

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in <i>NLRP</i> genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 differe ...[more]

PMID: 31601004

Similar Datasets

Project description:PurposeTo investigate the association of polymorphism of IL-1β rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1β for IDD.Patients and methodsA total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age (±3 years). The polymorphisms of IL-1β rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1β, MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student t-test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided P<0.10 were included in multivariate analysis, which employed a backward stepwise logistic regression model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value.ResultsMultivariate analysis showed that the polymorphism of IL-1β rs16944(T/C) was independently associated with IDD. The risk for IDD was significantly increased in TT and TC genotype compared with CC genotype, and the OR of TT genotype was higher than that of TC genotype. ANOVA analysis showed that serum concentration of IL-1β was highest in IL-1β rs16944 TT genotype, intermediate in TC genotype, and lowest in CC genotype. Similarly, serum concentrations of MMP-3 and ADAMTS-4 demonstrated the same tendency of TT > TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1β levels in predicting IDD was 0.788 (SE: 0.023, P=0.001, 95% CI: 0.742-0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%.ConclusionPolymorphism of IL-1β rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1β and subsequent stimulation of ECM degradation. IL-1β levels could be applied in predicting IDD.

Project description:ObjectiveThe aim of this study was to compare IL-1β levels in gingival crevicular fluid (GCF) from healthy and periodontitis sites of IL-1B(3954)-Single Nucleotide Polymorphism (SNP) positive and IL-1B(3954)-SNP negative periodontitis subjects in association with their bacterial profiles.BackgroundSusceptibility to periodontitis has been associated with several risk factors, including allelic variants at multiple gene loci. Variations in the IL-1 gene cluster have been linked with increased risk for periodontitis. IL-1B(3954)-SNP has been previously associated with increased levels of IL-1β in GCF or periodontal tissues in chronic periodontitis patients, as well as higher levels of specific periodontal pathogens. There is insufficient evidence to conclude if IL-1B gene polymorphisms affect the susceptibility to periodontitis by ultimately modulating the levels of IL-1β in GCF, the subgingival microbial profile or both.Materials and methodsGCF, subgingival plaque, and buccal epithelial cells were collected from 32 individuals with periodontitis. GCF IL-1β levels were measured by an enzyme-linked immunosorbent assay (ELISA). Bacterial plaque samples were analyzed for 11 periodontal pathogens using polymerase chain reaction (PCR) analysis with specific primers for the 16SrRNA gene of each bacterium. IL-1B(3954)-SNP status was determined by identifying the carriers of the polymorphic T allele.ResultsA significant association was shown between IL-1B(3954)-SNP and IL-1β GCF levels (amount and concentration). The concomitant presence of two or three red complex bacterial species was associated with increased IL-1β GCF levels in periodontitis sites (site-level analysis). The concurrent presence of all three red complex periodontal pathogens and IL-1B(3954)-SNP was associated with the highest IL-1β GCF levels in periodontitis sites.ConclusionsOur results indicate an independent association of both IL-1B(3954)-SNP and red complex bacterial species with increased IL-1β levels in GCF of periodontitis sites. A better understanding of the interaction between genetics, bacteria, and inflammation is essential to develop more effective diagnostic, prognostic, and therapeutic tools for periodontitis.

Project description:Interleukin-1β (IL-1β) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1β-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1β activity by blocking IL-1β-IL-1R1 interaction in OA. In this study, we report the anti-IL-1β activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1β-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1β-IL-1R1 interaction by direct binding to IL-1β using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1β bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1β-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1β-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1β-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1β-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1β-related diseases by hindering IL-1β-IL-1R1 interaction and suppressing IL-1β bioactivity.

Dataset Information

Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1? Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

Publications

Association of <i>NLRP1</i> Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets