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Toll-like receptor heterodimer variants protect from childhood asthma

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Presentation on theme: "Toll-like receptor heterodimer variants protect from childhood asthma"— Presentation transcript:

1 Toll-like receptor heterodimer variants protect from childhood asthma
Michael S.D. Kormann, PhD, Martin Depner, MSc, Dominik Hartl, MD, Norman Klopp, PhD, Thomas Illig, PhD, Jerzy Adamski, PhD, Christian Vogelberg, MD, Stephan K. Weiland, MD, Erika von Mutius, MD, Michael Kabesch, MD  Journal of Allergy and Clinical Immunology  Volume 122, Issue 1, Pages e8 (July 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 TLR1, TLR6, and TLR10 SNPs increase mRNA (A) and protein (B) expression on B cells (upper panel) and monocytes (lower panel) of respective TLRs when individuals carrying the homozygous rare alleles (n = 5) for TLR1_b, TLR6_a, and TLR10_b are compared with wild-type individuals (n = 9). Fig 1, A: Boxes represent medians ± interquartile range. Whiskers represent the minimum and maximum observations. Fig 1, B: Bars represent medians ± interquartile range of different donors. MFI, Median fluorescence intensity. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 TLR1, TLR6, and TLR10 SNPs increase proinflammatory and TH1-associated cytokine levels and reduce TH2-associated IL-4 expression after TLR2/1 and TLR2/6 stimulation. The secretion of TNF-α (A), IL-12 (B), IFN-γ (C), and IL-4 (D) was measured in culture supernatants by means of ELISA in triplicate. Bars represent medians ± interquartile range between different donors. LTA, Lipoteichoic acid; PGN, peptidoglycan. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Overview of cross-sectional and case-control selection based on children from ISAAC II (Munich and Dresden) and Leipzig. The original populations, all children with questionnaire data available,E3 that gave rise to both selections are shown. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Scheme of the selection algorithm used to select 21 putative functional SNPs in TLR1 through TLR10 for genotyping. ΔAA, Leads to amino acid change; ΔTF, affects transcription factor binding site; R2, correlation coefficient. ∗Previously reported to be directly or indirectly associated with the development of asthma. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 TLR1/TLR6/TLR10 gene loci on chromosome 4p14 and description of intragenetic and intergenetic LD patterns (r2 plots). Below are the positions of all frequent TLR1/TLR6/TLR10 SNPs (minor allele frequency > 0.1) and r2 plot in the European samples of the Innate Immunity Program for Genomic Applications mutation screen.E4 SNPs that were further investigated in this article are shown in bold red letters. CDS, Coding sequence; UTR, untranslated region. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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