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Association of genetic variations in the alpha1-antitrypsin and matrix metalloproteinase genes with lung function decline in a group of firefighters.

Yucesoy-B; Kurzius-Spencer-M; Johnson-VJ; Fluharty-K; Germolec-DR; Luster-MI; Burgess-JL
Toxicologist 2009 Mar; 108(1):289
The measurement of forced expiratory volume in 1 second (FEV1) and its decline over time are prognostic indicators of early chronic airflow obstruction. Although alpha1-antitrypsin (AAT) deficiency (Z allele) was shown to be a risk factor for rapid decline in lung function, individuals with the same AAT genotype may differ in their phenotypes suggesting the presence of other genetic modifiers. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes that play an important role in connective tissue remodeling and repair. The aim of this study was to investigate whether polymorphisms within genes encoding for AAT and MMPs may be associated with the age-related rate of FEV1 decline. Genetic variations in the AAT (Z, S and 3'), MMP-9 (IVS4+3G/T and 2003A/G) and MMP-12 (1082A/G and - 82A/G) genes were investigated in 374 active firefighters with at least five or more annual pulmonary function tests over a period of five or more years. Genotyping was performed using multiplex polymerase chain reaction (PCR) and 5' nucleasereal-time PCR assays. Rate of decline in FEV1 was calculated for each subject by running a simple linear regression of FEV1 over age. After adjusting for covariates, the AAT Z and 3' variants (both p=0.048) and the MMP12 -82A/G (p=0.009) polymorphism were associated with a more rapid rate of FEV1 decline. No association was observed between the rate of FEV1 decline and other variations. These data suggest that genetic variations within genes involved in tissue remodeling and repair may influence susceptibility to progressive decline in FEV1.
Age-factors; Biological-factors; Biological-effects; Chemical-hypersensitivity; Chemical-reactions; Fire-fighters; Fire-hazards; Genes; Genetic-factors; Genetics; Inhalation-studies; Lung; Lung-function; Lung-irritants; Occupational-exposure; Pulmonary-system-disorders; Respiration; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis
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Healthcare and Social Assistance; Services
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The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland