Epistatic effect of IL1A and IL4RA genes on the risk of atopy.

Several studies have demonstrated a linkage or association of the atopic phenotype with T-cell cytokine genes involved in the regulation of the TH1/TH2 balance (eg, IL4, IL13, and their common receptor, IL4RA). We have recently shown that polymorphism of the pro-inflammatory cytokine IL1A gene is strongly associated with atopy. We now examined whether the polymorphisms of IL1A (G/T at +4845) and IL4RA (T/C at +22446) would show an epistatic effect on the risk of atopy. Skin prick tests and gene polymorphism analyses were performed in a population-based sample of asthmatic and nonasthmatic subjects. Our results showed that in the nonasthmatic group the previously described elevated risk of atopy in noncarriers of allele T of IL1A (ie, having the genotype GG) was restricted to individuals who were also noncarriers of allele C of IL4RA (genotype TT). This finding applies to the general population of Finland, where 3.3% of adults are asthmatic. These data suggest that the IL1A and IL4RA genes show an epistatic effect on the risk of atopy.