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 (COPD). The objective of this study is to investigate the association of polymorphisms in asthma and COPD candidate genes with rates of lung function decline in a general population sample of aging men.
METHODS: We analyzed data from a cohort of 1047 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 divided into 2 groups, and we tested a total of 942 SNPs in 45 asthma and COPD candidate genes in the first group (testing cohort, n=545) for association with change in FEV₁ over time.
RESULTS: One hundred nineteen SNPs 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, 13 variants of 7 genes (DPP10, NPRS1,SFTPD, VDR/COL2A1, TGFB1/CCDC97,MMP12 and ADAM33) remained significantly associated with change in FEV₁ over time.
CONCLUSIONS: Our findings that genetic variants of genes involved in asthma and COPD are associated with lung function decline in normal aging subjects suggest that similar genetic mechanisms may underlie lung function decline in both disease and normal aging processes.This is a pre-copy-editing, author-produced PDF of an article accepted for publication in The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, following peer review. The published article is copyrighted by the Author(s) and published by Oxford University Press on behalf of The Gerontological Society of America. The definitive publisher-authenticated version [Poon, A. H., Houseman, E. A., Ryan, L., Sparrow, D., Vokonas, P. S., & Litonjua, A. A. (2014). Variants of Asthma and Chronic Obstructive Pulmonary Disease Genes and Lung Function Decline in Aging. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(7), 907-913. doi:10.1093/gerona/glt179] is available online at: http://biomedgerontology.oxfordjournals.org/content/69/7/907.abstractKeywords: Genetics, Normative aging, Successful aging, PulmonaryKeywords: Genetics, Normative aging, Successful aging, Pulmonar
