ST2L expression was increased in severe asthma (P = .02) and associated with multiple indicators of TH2-like inflammation, including blood eosinophils (P = .001), exhaled nitric oxide (P = .003), and epithelial CLCA1 (P < .0001) and eotaxin-3 (P = .001) mRNA expression.
We assessed in the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) whether IL1RL1 SNPs associate with levels of its soluble transcript IL1RL1 (IL1RL1-a) in serum, blood eosinophil counts, and asthma prevalence from birth to age 8 years, and whether IL1RL1-a serum levels associate with blood eosinophil counts.
Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002).
Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma.
Plasma and sputum IL-33, soluble ST2 (sST2) levels, and ST2L expression on eosinophils were measured in 10 healthy controls and 10 allergic asthmatics.
The critical function of IL-33/ST2 signaling in allergic inflammation is illustrated by the fact that IL33 and IL1RL1 are among the most highly replicated susceptibility loci for asthma.
Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.
IL-33 is likely to play a critical role in asthma because the IL33 and ST2/IL1RL1 genes have been reproducibly identified as major susceptibility loci in large-scale genome-wide association studies.
We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor-like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]-gasdermin A [GSDMA]).
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.
Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma.
Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.