Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)
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| Titel: | Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD) |
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| Autoren: | Petar Ozretić, Miguel Inacio da Silva Filho, Calogerina Catalano, Irena Sokolović, Andrea Vukić-Dugac, Maja Šutić, Matea Kurtović, Gordana Bubanović, Sanja Popović-Grle, Sanda Skrinjarić-Cincar, Oliver Vugrek, Irena Jukić, Lada Rumora, Martina Bosnar, Miroslav Samaržija, Robert Bals, Marko Jakopović, Asta Försti, Jelena Knežević |
| Quelle: | Genes (Basel) Genes Volume 10 Issue 10 |
| Verlagsinformationen: | MDPI AG, 2019. |
| Publikationsjahr: | 2019 |
| Schlagwörter: | Male, 0301 basic medicine, Nod Signaling Adaptor Proteins / metabolism, Interleukin-1beta, Kaplan-Meier Estimate, polymorphism, FEV1, Gene Frequency, Forced Expiratory Volume, Apoptosis Regulatory Proteins / metabolism, FEV1/FVC, Lung, Nod Signaling Adaptor Proteins / genetics, ddc:610, 0303 health sciences, Pulmonary Disease, Chronic Obstructive / physiopathology, Middle Aged, 3. Good health, Phenotype, Pulmonary Disease, Chronic Obstructive / genetics, COPD, NLRP, polymorphism, FEV1, FEV1/FVC, GOLD, serum IL-1β, Interleukin-1beta / analysis, Female, Adaptor Proteins, Signal Transducing / metabolism, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, Polymorphism, Single Nucleotide / genetics, COPD, NLRP, FEV1/FVC: GOLD, serum IL-1β, Gene Frequency / genetics, Genotype, NLR Proteins, Forced Expiratory Volume / genetics, Article, 03 medical and health sciences, Lung / pathology, Humans, Genetic Predisposition to Disease, GOLD, Alleles, Genetic Association Studies, Adaptor Proteins, Signal Transducing, Aged, Apoptosis Regulatory Proteins / genetics, Respiratory Function Tests / methods, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Basic Medical Sciences, Genetic Predisposition to Disease / genetics, Haplotypes, Case-Control Studies, Interleukin-1beta / blood, Nod Signaling Adaptor Proteins, Adaptor Proteins, Signal Transducing / genetics, Haplotypes / genetics, Apoptosis Regulatory Proteins |
| Beschreibung: | 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 NLRP 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 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-1β 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-1β 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. |
| Publikationsart: | Article Other literature type |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes10100783 |
| DOI: | 10.22028/d291-29797 |
| Zugangs-URL: | https://www.mdpi.com/2073-4425/10/10/783/pdf https://pubmed.ncbi.nlm.nih.gov/31601004 https://www.bib.irb.hr/1025843 https://doi.org/10.3390/genes10100783 https://repozitorij.unizg.hr/islandora/object/mef%3A2744 https://europepmc.org/article/MED/31601004 https://dabar.srce.hr/islandora/object/mef%3A2744 https://www.mdpi.com/2073-4425/10/10/783/pdf https://www.bib.irb.hr/1025843 http://fulir.irb.hr/5220/ http://fulir.irb.hr/5220/1/OzreticP_Association_Genes-10_2019_783.pdf https://urn.nsk.hr/urn:nbn:hr:184:898837 https://doi.org/10.3390/genes10100783 https://repository.medri.uniri.hr/islandora/object/medri:5131 https://urn.nsk.hr/urn:nbn:hr:184:898837 https://repository.medri.uniri.hr/islandora/object/medri:5131/datastream/FILE0 https://urn.nsk.hr/urn:nbn:hr:105:383052 https://doi.org/10.3390/genes10100783 |
| Rights: | CC BY |
| Dokumentencode: | edsair.doi.dedup.....dd7b4d27e3db54e21fe0c5bf3b448eb5 |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | 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-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP 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 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-1β 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-1β 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. |
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| ISSN: | 20734425 |
| DOI: | 10.3390/genes10100783 |