TNF-alpha (-308 G/A) and CD14 (-159T/C) polymorphisms in the bronchial responsiveness of Korean children with asthma.
BACKGROUND
TNF-alpha is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-alpha gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated by CD14(+) cells.


OBJECTIVE
We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism and examined the combined effect with CD14 (-159T/C) polymorphism in Korean children.


METHODS
Asthmatic (n = 788) and control (n = 153) children were evaluated for asthma phenotypes. Genotypes were determined by using the single-base extension method and PCR-restriction fragment length polymorphism.


RESULTS
There was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C). Significantly lower PC(20) values were seen in asthmatic (P = .016) children with the TNF-alpha risk allele (-308A). Higher frequencies of 1 or 2 copies of the risk allele were found in asthmatic children with moderate-to-severe BHR to methacholine and exercise compared with control children (adjusted odds ratio of 2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20], respectively). In addition, asthmatic children with risk alleles at both loci had significantly greater BHR than those homozygous for the common alleles (P = .018).


CONCLUSIONS
The TNF-alpha promoter polymorphism (-308G/A) might be associated with severe BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-alpha promoter (-308A) and CD14 promoter (-159C) polymorphisms in terms of BHR.


CONCLUSIONS
The TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene.
Hong
Soo-Jong
SJ
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Hyo-Bin
HB
Kang
Mi-Jin
MJ
Lee
So-Yeon
SY
Kim
Ja-Hyung
JH
Kim
Bong-Seong
BS
Jang
Seong-Ok
SO
Shin
Hyung-Doo
HD
Park
Choon-Sik
CS
D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha