A Dataset of 26 Candidate Gene and Pro-Inflammatory Cytokine Variants for Association Studies in Idiopathic Pulmonary Fibrosis: Frequency Distribution in Normal Czech Population

Kishore, Amit; Žižková, Veronika; Kocourková, Lenka; Petřek, Martin

doi:10.3389/fimmu.2015.00476

Cited by 13 publications

(7 citation statements)

References 44 publications

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“…Inflammatory cells release TGF-β, the key regulator of several profibrotic cytokines/chemokines, their receptors/subunits, and growth factors inducing epithelial-mesenchymal transition (EMT) ( 1 – 3 ). The pro-inflammatory and profibrotic cytokines involved in PF promote inflammation and irreversible damage to lung architecture with the loss of alveolar-capillary barrier basal membrane leading to persistent fibrosis ( 4 ). These pathogenic factors for PF have further been reported as associated with genetic factors including gene variants and non-coding regulatory microRNAs ( 3 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

2021

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This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

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Section: Introductionmentioning

confidence: 99%

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

2021

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“…The detailed procedures for the MassARRAY-based multiplexed assay design and iPLEX-based genotyping have been described previously ( 26 ). Briefly, the DNA template (10 ng) with multiplex primers and PCR mix (iPLEX ® Gold Reagent Set; Agena Bioscience) were used for single-base extension-based PCR amplification of the target region.…”

Section: Methodsmentioning

confidence: 99%

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

et al. 2021

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A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-β (TGF-β) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.

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“…The IPF cases were diagnosed as per ATS/ERS/JRS/ALAT guidelines ( 1 , 21 , 22 ) with typical clinical features and abnormalities on chest high-resolution computed tomography (HRCT) scans, abnormal lung function tests with reduced diffusing capacity of the lung for CO (DL CO ), and/or restrictive pulmonary deficit, exclusion of other known causes of interstitial lung disease (ILD). For comparisons of genotype, allele frequency, and carriage rate (phenotype frequency) of analyzed genomic variants and case–control association study, we have utilized the data on distribution of these variants in 96 Czech healthy controls ( 15 ). Genomic DNA was isolated from peripheral blood leukocytes by standard salting out method ( 23 ).…”

Section: Methodsmentioning

confidence: 99%

“…The details of the panel comprising 26 IPF candidate loci and genotyping procedure in IPF cases have been described previously ( 15 ). In brief, a total of 26 SNPs reported as associated with IPF in literature were selected.…”

Section: Methodsmentioning

confidence: 99%

“…In context of the above efforts, we have recently identified and reported 26 IPF-associated candidate loci ( 15 ). Besides characterizing their major functions, e.g., in regulating production of mucins ( MUC5B and MUC2 ) or of pro-inflammatory cytokines (IL-1, IL-8) and also in cell signaling and innate immunity processes ( TLR3 and TOLLIP ) involved in inflammatory and profibrotic pathways ( ), we have described the approach for their simultaneous investigation using a novel mass spectrometry based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) multiplexed genotyping assay and reported their gene frequencies in healthy Czech (European) population ( 15 ). There, we also suggested the wider application of the data from this report for association studies among genetically homogenous populations following the recommendation of STrengthening the REporting of Genetic Association studies (STREGA) ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

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Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations

et al. 2016

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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.

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A Dataset of 26 Candidate Gene and Pro-Inflammatory Cytokine Variants for Association Studies in Idiopathic Pulmonary Fibrosis: Frequency Distribution in Normal Czech Population

Cited by 13 publications

References 44 publications

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations

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