IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma.
Subgroup analyses found that the IL4RAI50V polymorphism was significantly associated with asthma risk in Asians (OR = 1.72, 95% CI 1.31-2.25, P<0.0001), pediatric asthma risk (OR = 1.50, 95% CI 1.13-1.99, P = 0.005), and atopic asthma risk (OR = 1.88, 95% CI 1.27-2.79, P = 0.002).
Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005).
Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).
The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population.