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

Abstract

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:

A GWAS 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 with TNFAIP3 and inhibits the TNF-α-induced nuclear factor κB inflammation pathway, were associated with asthma: rs1422673 (P = 3.44 × 10(-7)) and rs10036748 (P = 1.41 × 10(-6), r(2) = 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 T of rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. The minor allele T of 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 T allele 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.

• Authors: Xingnan Li, Elizabeth J Ampleford, Timothy D Howard, Wendy C Moore, Dara G Torgerson, Huashi Li, William W Busse, Mario Castro, Serpil C Erzurum, Elliot Israel, Dan L Nicolae, Carole Ober, Sally E Wenzel, Gregory A Hawkins, Eugene R Bleecker, Deborah A Meyers
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 130 Issue 4 Pg. 861-8.e7 (Oct 2012) ISSN: 1097-6825 [Electronic] United States
• PMID: 22694930 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• TNIP1 protein, human

Topics

• Asthma (etiology, genetics, immunology)
• Autoimmune Diseases (etiology, genetics, immunology)
• DNA-Binding Proteins (genetics)
• Genome-Wide Association Study
• Humans
• Polymorphism, Single Nucleotide