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Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma  Jocelyn.

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Presentation on theme: "Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma  Jocelyn."— Presentation transcript:

1 Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma  Jocelyn M. Biagini Myers, PhD, Lisa J. Martin, PhD, Melinda Butsch Kovacic, MPH, PhD, Tesfaye B. Mersha, PhD, Hua He, MS, Valentina Pilipenko, PhD, Mark A. Lindsey, BS, Mark B. Ericksen, MS, David I. Bernstein, MD, Grace K. LeMasters, PhD, James E. Lockey, MD, Gurjit K. Khurana Hershey, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 134, Issue 4, Pages e3 (October 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 LD (r2) among SNPs included in the gene-collapsing analyses for 407 asthmatic patients compared with 257 allergic control subjects in the white discovery GCPCR populations. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Epistasis of SPINK5 and TSLP. A, Discovery white GCPCR/GCC children. B, Replication of epistasis of SPINK5 and TSLP in replication GCPCR black children. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Hypothesized shared pathways leading to asthma and inflammation. A, SPINK5 overexpression increases levels of inflammatory cytokines. B, LEKTI deficiency increases KLK5/7/14 levels, activating through protease-activated receptor 2 (PAR2) and nuclear factor κB (NFkB), leading to TSLP production, and causing allergy and lung inflammation. C, LEKTI deficiency increases profillagrin cleavage compromising the skin barrier and contributing to sensitization and subsequent asthma. Solid lines represent published pathways, and dashed lines represent hypothesized pathways. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E1 LD of all TSLP, SPINK5, and FLG SNPs reported in analyses.
Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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