Association of cytokine gene polymorphisms with rate of decline in lung function.
OBJECTIVE
To investigate whether genetic variants involved in cytokine expression are associated with the age-related rate of decline in forced expiratory volume in 1 second (FEV1).


METHODS
Functional polymorphisms in the TNFalpha, TGF beta 1, IL-1 beta, IL-1RN, IL-13, and IL-8 genes were investigated in 374 active firefighters with at least five pulmonary function tests.


RESULTS
A protective effect was found between the presence of the TGF beta 1 -509 TT genotype and rate of decline in FEV1 (P = 0.043). Carrying an A allele at TNFalpha -308 (P = 0.010) and GG genotype at TNFalpha -238 (P = 0.028) was associated with a more rapid rate of FEV1 decline. The TNFalpha -308A/-238G haplotype was also associated with an increased rate of decline as compared with the other haplotypes.


CONCLUSIONS
Interindividual variability in progressive decline in FEV1 may be explained in part by genetic variations within genes involved in inflammatory responses.
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA. byucesoy@cdc.gov
Berran
B
Yucesoy
Margaret
M
Kurzius-Spencer
Victor J
VJ
Johnson
Kara
K
Fluharty
Michael L
ML
Kashon
Stefano
S
Guerra
Michael I
MI
Luster
Jefferey L
JL
Burgess
D000328:Adult; D000375:Aging / Q000502:physiology*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D018793:Interleukin-13; D053583:Interleukin-1beta; D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha