Néomi S. Grotenboer, MSc, Maria E. Ketelaar, MSc, Gerard H

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Presentation transcript:

Decoding asthma: Translating genetic variation in IL33 and IL1RL1 into disease pathophysiology Néomi S. Grotenboer, MSc, Maria E. Ketelaar, MSc, Gerard H. Koppelman, MD, PhD, Martijn C. Nawijn, PhD Journal of Allergy and Clinical Immunology Volume 131, Issue 3, Pages 856-865.e9 (March 2013) DOI: 10.1016/j.jaci.2012.11.028 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 LD of the polymorphisms located within the IL33 region (chromosome 9) and the IL1RL1/IL18R1 region (chromosome 2). A, LD plot of the IL33 region in the CEU population (see the Methods section in this article's Online Repository for more details). B, LD plot of the IL1RL1/IL18R1 region in the CEU population (see the Methods section in this article's Online Repository for more details). Asthma-associated polymorphisms are depicted in boldface, and expression quantitative trait loci are underlined. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 LD of the polymorphisms located within the IL33 region (chromosome 9) and the IL1RL1/IL18R1 region (chromosome 2). A, LD plot of the IL33 region in the CEU population (see the Methods section in this article's Online Repository for more details). B, LD plot of the IL1RL1/IL18R1 region in the CEU population (see the Methods section in this article's Online Repository for more details). Asthma-associated polymorphisms are depicted in boldface, and expression quantitative trait loci are underlined. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Biological activity of the IL-33/IL-1RL1 signaling pathway. IL-33–producing and responsive cells in the lung and the IL-33/IL-1RL1 signaling pathway (in part based on Lingel et al26) are shown. Airway epithelial damage will induce IL-33 release. IL-33 binding to a receptor complex of IL-1RL1-b and IL-1RAcP initiates recruitment of Mal or MyD88 signaling adaptor molecules, leading to activation of downstream pathways (lower insert). IL-1RL1-a can neutralize IL-33. In addition to its role in IL-33 signal transduction, IL-1RL1b can inhibit TLR signaling through TIR domain–dependent sequestration of the adaptor proteins MyD88 and Mal (top insert). Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 LD of the IL33 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 LD of the IL33 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 LD of the IL33 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 LD of the IL33 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 LD of the IL1RL1 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 LD of the IL1RL1 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 LD of the IL1RL1 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 LD of the IL1RL1 genomic region for the ASW, YRI, CHB, and MEX populations. A, ASW population. B, YRI population. C, CHB population. D, MEX population. Boldface, Asthma-associated SNPs; underlined, expression quantitative trait loci. Journal of Allergy and Clinical Immunology 2013 131, 856-865.e9DOI: (10.1016/j.jaci.2012.11.028) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions