Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases

摘要

Background: Genome-wide association studies (GWASs) of asthma have consistently implicated the ORM1-like 3 and gasdermin B (ORMDL3-GSDMB), IL33, IL-1 receptor-like 1 and IL-18 receptor 1 (IL1RL1-IL18R1), RAD50-IL13, thymic stromal lymphopoietin and WD repeat domain 36 region (TSLP-WDR36), and HLA-DR/DQ regions. Objective: AGWAS of asthma was performed in a non-Hispanic white population. Methods: A GWAS was performed in 813 Severe Asthma Research Program/Collaborative Studies on the Genetics of Asthma/Chicago Asthma Genetics Study cases and 1564 control subjects. The GWAS results were compared with those of the published GWASs of autoimmune diseases. Results: Multiple single nucleotide polymorphisms in the TNFAIP3 interacting protein 1 (TNIP1) gene, which interacts withTNFAIP3 and inhibits the TNF-α-induced nuclear factor kB inflammation pathway, were associated with asthma: rs1422673 (P = 3.44 × 10-7) and rs10036748 (P = 1.41 × 10-6, r2 = 0.67). rs1422673 was also associated with asthma in the published GABRIEL (P =.018) and EVE (P = 1.31 × 10-5) studies. The minor allele Tof rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. The minor allele Tof rs2395185 in HLA-DRA is the risk allele for asthma but the protective allele for ulcerative colitis. The minor allele A of rs2872507 in GSDMB is the protective allele for asthma but the risk allele for rheumatoid arthritis, Crohn disease, and ulcerative colitis. The Tallele of rs10036748 in the TNIP1 gene is the minor protective allele for asthma but the minor or major risk allele for systemic lupus erythematosus and systemic sclerosis in non-Hispanic white or Chinese subjects, respectively. Conclusions: Our study suggests that single nucleotide polymorphisms associated with both asthma and autoimmune diseases might have opposite effects on immunopathogenesis. (J Allergy Clin Immunol 2012;130:861-8.)