title: Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations.
abstract: 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.
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Amit
authors.initials: A
authors.lastname: Kishore
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Žižková
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Kocourková
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Petrkova
authors.affiliation: Laboratory of Pharmacology, University Hospital Alexandroupolis, Democritus University of Thrace , Athens , Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Bouros
authors.affiliation: Université Paris 13, COMUE Sorbonne Paris Cité, Bobigny , Paris , France.
authors.forename: Hilario
authors.initials: H
authors.lastname: Nunes
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Vladimíra
authors.initials: V
authors.lastname: Loštáková
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center, University of Freiburg , Freiburg , Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center, University of Freiburg , Freiburg , Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine and Dentistry, Palacký University , Olomouc , Czech Republic.
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kolek
authors.affiliation: Academic Department of Pneumonology, Hospital for Diseases of the Chest 'Sotiria', Medical School, University of Athens , Athens , Greece.
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.affiliation: Université Paris 13, COMUE Sorbonne Paris Cité, Bobigny , Paris , France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Petrek
keywords: MUC2; MUC5B; association study; cytokines; idiopathic pulmonary fibrosis; network analysis; sequenom MassARRAY; single nucleotide polymorphism