title: Multidrug resistance-associated protein 1 and lung function decline with or without long-term corticosteroids treatment in COPD.
abstract: Multidrug resistance-associated protein-1 (MRP1) reduces the oxidative stress generated by smoking, a risk factor for Chronic Obstructive Pulmonary Disease (COPD). We previously showed that MRP1 variants are associated with the level and decline of annual forced expiratory volume in one second (FEV(1)) in the general population. Moreover, we showed that MRP1 variants are also associated with FEV(1) level and inflammatory markers in COPD patients.We investigate in the current study the association of MRP1 protein expression in bronchial biopsies with FEV(1) decline in COPD patients using placebo, or inhaled corticosteroids (ICS) with or without long-acting β2-agonists. Additionally we investigate the association of MRP1 variants with FEV(1) decline. MRP1 variants (rs212093, rs4148382, rs504348, rs4781699, rs35621) were genotyped in 110 COPD patients. Associations of MRP1 variants and MRP1 protein expression in bronchial biopsies (obtained at baseline, 6 and 30 months) with FEV(1) decline were analyzed using linear mixed-effect models. During 30-month ICS treatment, subjects with a moderate staining for MRP1 had less FEV(1) decline than those with a weak staining. In subjects stopping ICS after 6 months followed by 24-month placebo, moderate staining for MRP1 was associated with faster FEV(1) decline than in those with a weak staining. None of the variants was associated with FEV(1) decline. Our unique study suggests a role of MRP1 protein expression in bronchial biopsies in FEV(1) decline occurring selectively in COPD patients with long-term (30-month) ICS therapy.
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands. s.budulac@umcg.nl
authors.forename: Simona E
authors.initials: SE
authors.lastname: Budulac
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Thérèse S
authors.initials: TS
authors.lastname: Lapperre
authors.forename: Lisette I Z
authors.initials: LI
authors.lastname: Kunz
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.forename: H
authors.initials: H
authors.lastname: Marike Boezen
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology*; D000068299:Salmeterol Xinafoate
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068298:Fluticasone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000068299:Salmeterol Xinafoate; C421109:multidrug resistance-associated protein 1