title: Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications.
abstract: Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation not fully reversible. However, a number of patients with COPD respond to bronchodilator agents. Some studies have shown polymorphisms in the b2-adrenergic (ADRb2) and muscarinic M2 and M3 receptors (CHRM) that may participate in the modulation of the receptor responses. This study was designed to investigate the existence and the role of adrenergic and muscarinic receptor polymorphisms and their functional impact in COPD. Eighty-two patients with COPD and 17 healthy smokers were recruited and screened for ADRb2 (T164I and R175R), for CHRM2 (rs1824024) and for CHRM3 (-513C/A and -492C/T). Among the polymorphisms studied our results was not able to demonstrate statistically significant association between the polymorphisms studied and COPD risk. Contrarily, we identified, in our COPD population, a significant association with the CHRM2 (rs1824024) polymorphism and disease severity, with lower lung function test values, frequent exacerbations, and poor response to anti-cholinergic drugs. These results suggest the potential role of receptor polymorphism assessment to discriminate newly COPD phenotypes. J. Cell. Physiol. 231: 1745-1751, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cherubini
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Esposito
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Scozzi
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Terzo
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Giorgia Amira
authors.initials: GA
authors.lastname: Osman
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mariotta
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Mancini
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Pierdonato
authors.initials: P
authors.lastname: Bruno
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Division of Pulmonology, AO Sant' Andrea, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ricci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D043587:Receptor, Muscarinic M3; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D011976:Receptors, Muscarinic / Q000235:genetics; D012129:Respiratory Function Tests; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C553443:ADRB2 protein, human; D001993:Bronchodilator Agents; C487078:CHRM2 protein, human; C000595896:CHRM3 protein, human; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic