title: Variants of asthma and chronic obstructive pulmonary disease genes and lung function decline in aging.
abstract: BACKGROUND
  A substantial proportion of the general population has low lung function, and lung function is known to decrease as we age. Low lung function is a feature of several pulmonary disorders, such as uncontrolled asthma and chronic obstructive pulmonary disease. The objective of this study is to investigate the association of polymorphisms in asthma and chronic obstructive pulmonary disease candidate genes with rates of lung function decline in a general population sample of aging men.
  
  
  METHODS
  We analyzed data from a cohort of 1,047 Caucasian men without known lung disease, who had a mean of 25 years of lung function data, and on whom DNA was available. The cohort was randomly divided into two groups, and we tested a total of 940 single-nucleotide polymorphisms in 44 asthma and chronic obstructive pulmonary disease candidate genes in the first group (testing cohort, n = 545) for association with change in forced expiratory volume in 1 second over time.
  
  
  RESULTS
  One hundred nineteen single-nucleotide polymorphisms that showed nominal associations in the testing cohort were then genotyped and tested in the second group (replication cohort, n = 502). Evidence for association from the testing and replication cohorts were combined, and after adjustment for multiple testing, seven variants of three genes (DPP10, NPSR1, and ADAM33) remained significantly associated with change in forced expiratory volume in 1 second over time.
  
  
  CONCLUSIONS
  Our findings that genetic variants of genes involved in asthma and chronic obstructive pulmonary disease are associated with lung function decline in normal aging participants suggest that similar genetic mechanisms may underlie lung function decline in both disease and normal aging processes.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts. Meakins Christie Laboratories, McGill University Health Centre (MUHC), Montreal, Quebec, Canada.
authors.forename: Audrey H
authors.initials: AH
authors.lastname: Poon
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Corvallis.
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.affiliation: Division of Mathematics, Informatics and Statistics (CMIS), Commonwealth Scientic and Industrial Research Organisation (CSIRO), North Ryde, New South Wales, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Ryan
authors.affiliation: Normative Aging Study, VA Boston Healthcare System, Massachusetts. Department of Medicine at Boston University School of Medicine, Masssachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: Normative Aging Study, VA Boston Healthcare System, Massachusetts. Department of Medicine at Boston University School of Medicine, Masssachusetts.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. augusto.litonjua@channing.harvard.edu.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology*; D015331:Cohort Studies; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics; D005541:Forced Expiratory Volume / Q000235:genetics* / Q000502:physiology*; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D055815:Young Adult
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; C476879:DPP10 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D051722:ADAM Proteins; C450441:ADAM33 protein, human
keywords: Genetics; Normative aging; Pulmonary; Successful aging.