Epistatic effect of TLR4 and IL4 genes on the risk of asthma in females.
BACKGROUND
Many studies have demonstrated a connection between asthma and T-cell cytokine genes, such as genes coding for interleukin-4 (IL4) and IL-13, which are involved in the regulation of the TH1/TH2 balance. The toll-like receptor 4 (TLR4), the principal receptor for bacterial endotoxin, has attracted attention as a potential risk factor for asthma. We examined whether the polymorphisms of the TLR4 (A/G at +896) and IL4 (C/T at -590) showed an epistatic effect on the risk of asthma or atopy.


METHODS
Gene polymorphism analyses and skin prick tests were performed on asthmatic and nonasthmatic adult subjects of a Finnish population-based case-control study. The phenotype studied was persistent asthma.


RESULTS
The results showed that genotypes of neither the TLR4 SNP at +896 nor IL4 SNP at -590 were separately found to be associated with asthma. However, the female carriers of allele G (i.e. genotype AG or GG) of TLR4 and allele T (genotype CT or TT) of IL4 had a significantly increased risk for asthma. No association of these genes and atopy was found.


CONCLUSIONS
Our results indicate that in females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma. The low LPS-responsive allele G of TLR4 and high IgE production allele T of IL4 were found to be the predisposing combination. However, there was no epistatic effect on the risk of atopy.
Adjers
Kati
K
Department of Microbiology and Immunology, Medical School, University of Tampere, Tampere, Finland. kati.adjers@uta.fi
Karjalainen
Jussi
J
Pessi
Tanja
T
Eklund
Carita
C
Hurme
Mikko
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D044465:White People
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D015847:Interleukin-4