Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Without internal affiliation

DOI

  • Author: Jespersgaard, Cathrine

    Statens Serum Institut

  • Author: Fode, Peder

    Statens Serum Institut

  • Author: Dybdahl, Marianne

    Statens Serum Institut

  • Author: Vind, Ida

    University of Copenhagen

  • Author: Nielsen, Ole Haagen

    University of Copenhagen

  • Author: Csillag, Claudio

    University of Copenhagen

  • Author: Munkholm, Pia

    University of Copenhagen

  • Author: Vainer, Ben

    University of Copenhagen

  • Author: Riis, Lene

    University of Copenhagen

  • Author: Elkjaer, Margarita

    University of Copenhagen

  • Author: Pedersen, Natalia

    University of Copenhagen

  • Author: Knudsen, Elisabeth

    University of Copenhagen

  • Author: Andersen, Paal Skytt

    Statens Serum Institut

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Background and Purpose of Study Extensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1-3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn's disease (CD) patients and the possible genetic association of DEFA1A3 with CD. Methods Two-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy number of DEFA1A3 and individual alleles, DEFA1 and DEFA3, were compared with those for controls, by use of combined real-time quantitative PCR and pyrosequencing, and correlated with disease location. Results Inflammatory-dependent mRNA expression of DEFA1A3 (P<0.001), and the presence of alpha-defensin peptides, were observed in colonic tissue samples. Higher DEFA1A3 gene copy number (CD: mean copy number, 7.2 vs. controls 6.7; P<0.001) and individual DEFA1 alleles (CD mean copy number 5.6 vs. controls 5.1; P<0.01) were associated with CD, with strong association with colonic location (P<0.001). Conclusions Alpha-defensins are involved in the inflammation of CD, with local mRNA and peptide expression. In combination with the findings that a high DEFA1A3 copy number is significantly linked to CD, these results suggest that a high DEFA1A3 copy number might be important in hindering the normal inflammatory response in CD, particularly colonic CD.

Original languageEnglish
JournalDigestive Diseases and Sciences
Volume56
Issue number12
Pages (from-to)3517-3524
Number of pages8
ISSN0163-2116
DOIs
StatePublished - Dec 2011
Externally publishedYes
CitationsWeb of Science® Times Cited: 15

    Keywords

  • Colonic tissue, Copy number variation, Crohn's disease, Defensin, Genetic association, Real-time PCR
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