Variants of asthma and chronic obstructive pulmonary disease genes and lung function decline in aging

J Gerontol A Biol Sci Med Sci. 2014 Jul;69(7):907-13. doi: 10.1093/gerona/glt179. Epub 2013 Nov 19.


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.

Keywords: Genetics; Normative aging; Pulmonary; Successful aging..

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ADAM Proteins / genetics
  • Adult
  • Aged
  • Aging / genetics*
  • Aging / physiology*
  • Asthma / genetics*
  • Asthma / physiopathology*
  • Cohort Studies
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Forced Expiratory Volume / genetics*
  • Forced Expiratory Volume / physiology*
  • Genetic Association Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Receptors, G-Protein-Coupled / genetics
  • Young Adult


  • NPSR1 protein, human
  • Receptors, G-Protein-Coupled
  • DPP10 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • ADAM Proteins
  • ADAM33 protein, human