Susceptibility genes for rapid decline of lung function in the lung health study

A. J. Sandford, T. Chagani, T. D. Weir, J. E. Connett, N. R. Anthonisen, P. D. Paré

Research output: Contribution to journalArticlepeer-review

254 Scopus citations

Abstract

The genes that contribute to the genetic susceptibility to chronic obstructive pulmonary disease (COPD) remain largely unknown. We hypothesized that widely divergent rates of decline in lung function in smokers would be a robust phenotype for detection of genes that contribute to COPD severity. We selected 283 rapid decliners (ΔFEV1 = -154 ± 3 ml/yr) and 308 nondecliners (ΔFEV1 = +15 ± 2 ml/yr) from among smokers followed for 5 yr in the NHLBI Lung Health Study. Rapid decline of FEV1 was associated with the MZ genotype of the α1-antitrypsin gene (odds ratio [OR] = 2.8, p = 0.03). This association was stronger for a combination of a family history of COPD with MZ (OR = 9.7, p = 0.03). These data suggest that the MZ genotype results in an increased rate of decline in lung function and interacts with other familial factors. Haplotype frequencies of the microsomal epoxide hydrolase (mEH) gene were significantly different between rapid decliners and nondecliners (p = 0.03). A combination of a family history of COPD with homozygosity for the His113/His139 mEH haplotype was also associated with rapid decline of lung function (OR = 4.9, p = 0.04). The α1-antitrypsin S and 3′ polymorphisms, vitamin D-binding protein isoforms, and tumor necrosis factor (TNF-α G-308A and TNF-β A252G) polymorphisms were not associated with rate of decline of lung function.

Original languageEnglish (US)
Pages (from-to)469-473
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume163
Issue number2
DOIs
StatePublished - 2001

Fingerprint

Dive into the research topics of 'Susceptibility genes for rapid decline of lung function in the lung health study'. Together they form a unique fingerprint.

Cite this