1. Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)
- Author
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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, and Jelena Knežević
- Subjects
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 - 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-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.
- Published
- 2019