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

Autor: Martina Bosnar, Gordana Bubanović, Oliver Vugrek, Calogerina Catalano, Petar Ozretić, Miguel Inacio da Silva Filho, Lada Rumora, Sanda Škrinjarić-Cincar, Sanja Popović-Grle, Matea Kurtović, Marko Jakopović, Maja Šutić, Irena Jukić, Robert Bals, Andrea Vukić-Dugac, Astra Försti, Irena Sokolovic, Miroslav Samaržija, Jelena Knežević
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Nod Signaling Adaptor Proteins / metabolism
Kaplan-Meier Estimate
Gastroenterology
polymorphism
Pathogenesis
FEV1
0302 clinical medicine
Apoptosis Regulatory Proteins / metabolism
Genetics (clinical)
Nod Signaling Adaptor Proteins / genetics
nlrp
COPD
Pulmonary Disease
Chronic Obstructive / physiopathology
respiratory system
Middle Aged
GOLD [FEV1/FVC]
Obstructive lung disease
3. Good health
Phenotype
Pulmonary Disease
Chronic Obstructive / genetics
COPD
NLRP
polymorphism
FEV1
FEV1/FVC
GOLD
serum IL-1β
Female
Interleukin-1beta / analysis
Adaptor Proteins
Signal Transducing / metabolism
BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti
Polymorphism
Single Nucleotide / genetics
medicine.medical_specialty
NLRP
FEV1/FVC: GOLD
serum IL-1β
Gene Frequency / genetics
Genotype
lcsh:QH426-470
fev1/fvc
Single-nucleotide polymorphism
Forced Expiratory Volume / genetics
03 medical and health sciences
FEV1/FVC ratio
Lung / pathology
Internal medicine
Genetics
medicine
Humans
Allele
Alleles
Genetic Association Studies
Aged
Apoptosis Regulatory Proteins / genetics
business.industry
Respiratory Function Tests / methods
BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences
Case-control study
Basic Medical Sciences
gold
medicine.disease
Genetic Predisposition to Disease / genetics
respiratory tract diseases
Minor allele frequency
lcsh:Genetics
030104 developmental biology
030228 respiratory system
Case-Control Studies
Interleukin-1beta / blood
Adaptor Proteins
Signal Transducing / genetics
Haplotypes / genetics
fev1
business
Zdroj: Genes
Genes, Vol 10, Iss 10, p 783 (2019)
Volume 10
Issue 10
ISSN: 2073-4425
Popis: 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&beta
induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1&beta
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&rsquo
overall survival was analyzed with the Kaplan&ndash
Meier method with the log-rank test. Serum IL-1&beta
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&beta
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.
Databáze: OpenAIRE
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