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

TitleSusceptibility genes for rapid decline of lung function in the lung health study.
Publication TypeJournal Article
Year of Publication2001
AuthorsSandford, AJ, Chagani, T, Weir, TD, Connett, JE, Anthonisen, NR, Paré, PD
JournalAm J Respir Crit Care Med
Volume163
Issue2
Pagination469-73
Date Published2001 Feb
ISSN1073-449X
KeywordsAdult, Epoxide Hydrolases, Female, Forced Expiratory Volume, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Lung Diseases, Obstructive, Lymphotoxin-alpha, Male, Middle Aged, Phenotype, Polymorphism, Genetic, Risk Factors, Smoking, Tumor Necrosis Factor-alpha, Vitamin D-Binding Protein
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 (deltaFEV1 = -154 +/- 3 ml/yr) and 308 nondecliners (deltaFEV1 = +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 alpha1-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 alpha1-antitrypsin S and 3' polymorphisms, vitamin D-binding protein isoforms, and tumor necrosis factor (TNF-alpha G-308A and TNF-beta A252G) polymorphisms were not associated with rate of decline of lung function.

DOI10.1164/ajrccm.163.2.2006158
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID11179124