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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)
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

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