Genetic risk factors for accelerated lung function decline over time.
Yucesoy-B; Kurzius-Spencer-M; Johnson-VJ; Fluharty-K; Kashon-ML; Guerra-S; Luster-MI; Burgess-JL
Am J Respir Crit Care Med 2008 Apr; 177(Meeting Abstracts):A908
Objective: The measurement of forced expiratory volume in 1 second (FEV1) and its decline over time are prognostic indicators of early chronic airflow obstruction resulting in various pulmonary and cardiovascular diseases. The aim of this study was to investigate whether genetic variants within genes encoding for cytokines may be associated with the age-related rate of FEV1 decline. Methods: Single nucleotide polymorphisms (SNPs) in the TNF, TGF1, IL-1, IL-1RN, IL-13 and IL-8 genes were investigated in 374 active firefighters with at least five pulmonary function tests. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism and 5 nuclease real-time PCR assays. Rate of decline in FEV1 was calculated for each subject by running a simple linear regression of FEV1 over age. Multiple linear regression analyses adjusted for potential confounders were run to evaluate the association of specific genotypes with the rate of FEV1 decline. Results: After adjusting for covariates, a protective effect was found between the presence of the TGF1 -509 TT genotype and rate of decline in FEV1 (p=0.043). Carrying an A allele at TNF -308 (p=0.010) and GG genotype at TNF -238 (p=0.028) were associated with a more rapid rate of FEV1 decline. The TNF -308A/-238G haplotype was associated with more rapid decline as compared with the referent -308G/-238G haplotype (p=0.031). The IL-1RN +2018 TT genotype was associated with a steeper rate of decline (p=0.052). Conclusions: Inter-individual variability in progressive decline in FEV1 may be explained in part by genetic variations within genes involved in inflammatory responses.
Genetic-factors; Genetics; Genes; Respiratory-system-disorders; Pulmonary-system-disorders; Pulmonary-function; Cardiovascular-function; Cardiovascular-system-disease; Cardiovascular-system-disorders; Cardiopulmonary-function; Cardiopulmonary-system; Humans
American Journal of Respiratory and Critical Care Medicine