Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10(-11)]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10(-4)] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10(-5)]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

Academic Department of Pneumonology Hospital for Diseases of the Chest 'Sotiria' Medical School University of Athens Athens Greece

Department of Pneumology Center for Medicine Medical Center University of Freiburg Freiburg Germany

Department of Respiratory Medicine Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

Laboratory of Immunogenomics Department of Pathological Physiology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

Laboratory of Immunogenomics Department of Pathological Physiology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic; Faculty of Medicine and Dentistry Institute of Molecular and Translational Medicine Palacký University and Faculty Hospital Olomouc Czech Republic

Laboratory of Pharmacology University Hospital Alexandroupolis Democritus University of Thrace Athens Greece

Université Paris 13 COMUE Sorbonne Paris Cité Bobigny Paris France

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