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Open AccessArticle

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

1
Ruđer Bošković Institute, Division of Molecular Medicine, 10 000 Zagreb, Croatia
2
Division of Molecular Genetic Epidemiology, DKFZ, 69 120 Heidelberg, Germany
3
Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia
4
Josip Juraj Strossmayer University of Osijek, School of Medicine, 31 000 Osijek, Croatia
5
Department of Pulmology, Universitiy Hospital Center Osijek, 31 000 Osijek, Croatia
6
Croatian Institute of Transfusion Medicine, 10 000 Zagreb, Croatia
7
Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia
8
Fidelta d.o.o., Prilaz baruna Filipovića 29, 10 000 Zagreb, Croatia
9
Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University, 66 424 Homburg, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
These authors share senior authorship.
Genes 2019, 10(10), 783; https://doi.org/10.3390/genes10100783
Received: 13 July 2019 / Revised: 5 September 2019 / Accepted: 1 October 2019 / Published: 9 October 2019
(This article belongs to the Section Human Genomics and Genetic Diseases)
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.
Keywords: COPD, NLRP, polymorphism, FEV1, FEV1/FVC, GOLD, serum IL-1β COPD, NLRP, polymorphism, FEV1, FEV1/FVC, GOLD, serum IL-1β
MDPI and ACS Style

Ozretić, P.; da Silva Filho, M.I.; Catalano, C.; Sokolović, I.; Vukić-Dugac, A.; Šutić, M.; Kurtović, M.; Bubanović, G.; Popović-Grle, S.; Skrinjarić-Cincar, S.; Vugrek, O.; Jukić, I.; Rumora, L.; Bosnar, M.; Samaržija, M.; Bals, R.; Jakopović, M.; Försti, A.; Knežević, J. Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD). Genes 2019, 10, 783.

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