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01.12.2011 | Original Article

Alpha-Defensin DEFA1A3 Gene Copy Number Elevation in Danish Crohn’s Disease Patients

verfasst von: Cathrine Jespersgaard, Peder Fode, Marianne Dybdahl, Ida Vind, Ole Haagen Nielsen, Claudio Csillag, Pia Munkholm, Ben Vainer, Lene Riis, Margarita Elkjaer, Natalia Pedersen, Elisabeth Knudsen, Paal Skytt Andersen

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2011

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Abstract

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.

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Titel: Alpha-Defensin DEFA1A3 Gene Copy Number Elevation in Danish Crohn’s Disease Patients
verfasst von: Cathrine Jespersgaard
Peder Fode
Marianne Dybdahl
Ida Vind
Ole Haagen Nielsen
Claudio Csillag
Pia Munkholm
Ben Vainer
Lene Riis
Margarita Elkjaer
Natalia Pedersen
Elisabeth Knudsen
Paal Skytt Andersen
Publikationsdatum: 01.12.2011
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2011
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-011-1794-8

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