Gene-gene synergistic effect on atopic asthma: tumour necrosis factor-alpha-308 and lymphotoxin-alpha-NcoI in Taiwan's children.
BACKGROUND
Asthma is now known to be an inflammatory response caused by the release of inflammatory mediators and cytokines. Tumour necrosis factor (TNF) is a potent cytokine in the inflammation response of the airway, and the polymorphisms of TNF genes have been associated with asthma.


OBJECTIVE
This study investigated two variants, TNF-alpha-308*2 and lymphotoxin (LT)-alpha-NcoI*1, which may predispose individuals to asthma and atopy pathogenesis.


METHODS
PCR-based assays were performed to determine LT-alpha-NcoI*1 and TNF-alpha-308*2 genotypes among our subjects, with 128 atopic asthmatics and 51 non-atopic asthmatics, 55 atopic controls, and 78 non-atopic controls in this genetic case-control study.


RESULTS
The TNF-alpha-308*2 polymorphism increased in subjects with atopic asthma vs. non-atopic controls after adjusting for age distribution (adjusted odds ratios, AOR=2.73, 95% confidence interval, CI=1.16-6.64), but was not associated with non-atopic asthma (AOR=2.40, 95% CI=0.81-7.09). LT-alpha-NcoI*1 did not show an independent association with either atopic asthma or any one phenotype of specific IgE. The synergistic effect between these two genes was conducted, and the interaction between TNF-alpha-308*2 and LT-alpha-NcoI*1 polymorphisms was seen for atopic asthma (OR=2.59, 95% CI=1.10-6.10) when compared with all controls.


CONCLUSIONS
We have concluded that TNF-alpha-308 may be a risk factor for atopic asthma, whereas the LT-alpha-NcoI polymorphism may modify risk to atopic asthma with TNF-alpha-308.
School of Public Health, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
T-N
TN
Wang
W-Y
WY
Chen
T-H
TH
Wang
C-J
CJ
Chen
L-Y
LY
Huang
Y-C
YC
Ko
D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D016015:Logistic Models; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012306:Risk; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha