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doi:10.22028/D291-29797
Titel: | Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD) |
VerfasserIn: | Ozretić, Petar da Silva Filho, Miguel Inacio Catalano, Calogerina Sokolović, Irena Vukić-Dugac, Andrea Šutić, Maja Kurtović, Matea Bubanović, Gordana Popović-Grle, Sanja Skrinjarić-Cincar, Sanda Vugrek, Oliver Jukić, Irena Rumora, Lada Bosnar, Martina Samaržija, Miroslav Bals, Robert Jakopović, Marko Försti, Asta Knežević, Jelena |
Sprache: | Englisch |
Titel: | Genes |
Bandnummer: | 10 |
Heft: | 10 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2019 |
Freie Schlagwörter: | COPD NLRP polymorphism FEV1 FEV1/FVC GOLD serum IL-1β |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
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. |
DOI der Erstveröffentlichung: | 10.3390/genes10100783 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-297976 hdl:20.500.11880/30060 http://dx.doi.org/10.22028/D291-29797 |
ISSN: | 2073-4425 |
Datum des Eintrags: | 19-Nov-2020 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Materials |
In Beziehung stehendes Objekt: | http://www.mdpi.com/2073-4425/10/10/783/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Innere Medizin |
Professur: | M - Prof. Dr. Robert Bals |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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genes-10-00783-v2.pdf | 1,28 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons