Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis: Part A.

Autor: Wiertz IA; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Moll SA; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Seeliger B; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), 30265 Hannover, Germany., Barlo NP; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., van der Vis JJ; Department of Medical Microbiology and Immunology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Korthagen NM; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Rijkers GT; Department of Medical Microbiology and Immunology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Ruven HJT; Department of Clinical Chemistry, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands., Grutters JC; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands.; Division Heart & Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Prasse A; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), 30265 Hannover, Germany.; Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany., van Moorsel CHM; Centre for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2020 Jun 21; Vol. 9 (6). Date of Electronic Publication: 2020 Jun 21.
DOI: 10.3390/jcm9061940
Abstrakt: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease, characterized by fibroblast proliferation and extracellular matrix deposition. CC-chemokine ligand 18 (CCL18) upregulates the production of collagen by lung fibroblasts and is associated with mortality. This study was designed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the CCL18 gene on CCL18 expression and survival in IPF. Serum CCL18 levels and four SNPs in the CCL18 gene were analyzed in 77 Dutch IPF patients and 349 healthy controls (HCs). CCL18 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 18 healthy subjects. Survival analysis was conducted, dependent on CCL18-levels and -genotypes and validated in two German IPF cohorts (Part B). IPF patients demonstrated significantly higher serum CCL18 levels than the healthy controls ( p < 0.001). Both in IPF patients and HCs, serum CCL18 levels were influenced by rs2015086 C > T genotype, with the highest CCL18-levels with the presence of the C-allele. Constitutive CCL18 mRNA-expression in PBMCs was significantly increased with the C-allele and correlated with serum CCL18-levels. In IPF, high serum levels correlated with decreased survival ( p = 0.02). Survival was worse with the CT-genotype compared to the TT genotype ( p = 0.01). Concluding, genetic variability in the CCL18 -gene accounts for differences in CCL18 mRNA-expression and serum-levels and influences survival in IPF.
Databáze: MEDLINE
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