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. Copyright (c) 2005 S. Karger AG, Basel.
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. Copyright (c) 2005 S. Karger AG, Basel.