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Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion  Anna Lluis, MSc, Michaela Schedel,

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Presentation on theme: "Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion  Anna Lluis, MSc, Michaela Schedel,"— Presentation transcript:

1 Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion  Anna Lluis, MSc, Michaela Schedel, PhD, Jing Liu, MD, Sabina Illi, PhD, Martin Depner, MSc, Erika von Mutius, MD, Michael Kabesch, MD, Bianca Schaub, MD  Journal of Allergy and Clinical Immunology  Volume 127, Issue 6, Pages e6 (June 2011) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Genomic structure, localization, and linkage disequilibrium (R2 plot) of the genotyped polymorphisms in the 17q21 locus. Arrows indicate transcriptional direction. Exons with exon numbers are displayed in color codes. Smaller red boxes represent 5′ and 3′ untranslated regions. Tagging SNPs (R2 > 0.85) for each linkage disequilibrium block (brackets) are depicted in boldface. Chr, Chromosome; Mb, Megabase. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 ORMDL3 and GSDMA gene expression was increased in carriers of 17q21 risk alleles (black bars) in comparison with nonrisk alleles (white bars) after Der p 1 stimulation in CBMCs. A and B, rs , n = 13/11. ΔCT values are shown; axes are vice versa; lower ΔCT values between groups correspond to increased mRNA expression. Data are shown as median (± interquartile range); P values are calculated by the Wilcoxon test. Gene expression on mRNA levels was assessed in subjects homozygous for the risk or nonrisk alleles. PHA, Phytohemagglutinin; Ppg, peptidoglycan; U, unstimulated. ∗Significance of P ≤ .004 (below the multiple testing significance threshold). Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 A-F, ORMDL3 and GSDMA gene expression was increased in homozygous carriers of the risk haplotype (black bars) in comparison with the nonrisk haplotype (white bars) after Der p 1 and/or phytohemagglutinin (PHA) stimulation in CBMCs. mRNA expression of genes located in 17q21 locus (n = 9/8). ΔCT values are shown; axes are vice versa; lower ΔCT values between groups correspond to increased mRNA expression. Data are shown as median (± interquartile range), analyzed applying the Wilcoxon test. mRNA expression was assessed in subjects homozygous for the risk or the nonrisk haplotype. Ppg, Peptidoglycan; U, unstimulated. ∗Significance of P ≤ .004 (below the multiple testing significance threshold). Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 ORMDL3 expression in CBMCs and PBMCs. mRNA expression of ORMDL3 was assessed in CBMCs (n = 25) and PBMCs (n = 18) by real-time RT-PCR. Data are shown as median (± interquartile range), analyzed applying the Wilcoxon (A) or the signed rank test (B and C); axes are vice versa. PHA, Phytohemagglutinin; Ppg, peptidoglycan; U, unstimulated. Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E1 ORMDL3 and GSDMA gene expression was increased in carriers of 17q21 risk alleles (black bars) in comparison with nonrisk alleles (white bars) after Der p 1 stimulation in CBMCs. A and D, rs , n = 12/11. B and E, rs , n = 10/10. C and F, rs , n = 9/10. ΔCT values are shown; axes are vice versa; lower ΔCT values between groups correspond to increased mRNA expression. Data are shown as median (± interquartile range). P values are calculated by the Wilcoxon test. Gene expression was assessed in subjects homozygous for the risk or nonrisk alleles. PHA, Phytohemagglutinin; Ppg, peptidoglycan; U, unstimulated. ∗Significance of P ≤ .004 (below the multiple testing significance threshold). Journal of Allergy and Clinical Immunology  , e6DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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