caa a22 4500 445794690 CHVBK 20180317145121.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10620-011-1794-8 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1794-8 Alpha-Defensin DEFA1A3 Gene Copy Number Elevation in Danish Crohn's Disease Patients [Elektronische Daten] [Cathrine Jespersgaard, Peder Fode, Marianne Dybdahl, Ida Vind, Ole Nielsen, Claudio Csillag, Pia Munkholm, Ben Vainer, Lene Riis, Margarita Elkjaer, Natalia Pedersen, Elisabeth Knudsen, Paal Andersen] 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. Springer Science+Business Media, LLC, 2011 Crohn's disease nationallicence Colonic tissue nationallicence Copy number variation nationallicence Defensin nationallicence Genetic association nationallicence Real-time PCR nationallicence Jespersgaard Cathrine Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark aut Fode Peder Laboratory for Microbial Pathogenesis and Host Susceptibility, Department for Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark aut Dybdahl Marianne Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark aut Vind Ida Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Nielsen Ole Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Csillag Claudio Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Munkholm Pia Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Vainer Ben Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark aut Riis Lene Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Elkjaer Margarita Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Pedersen Natalia Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut Knudsen Elisabeth Department of Gastroenterology, Glostrup University Hospital, Glostrup, Denmark aut Andersen Paal Laboratory for Microbial Pathogenesis and Host Susceptibility, Department for Microbiological Surveillance and Research, Statens Serum Institut, 5 Artillerivej, 2300, Copenhagen S, Denmark aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/12(2011-12-01), 3517-3524 0163-2116 56:12<3517 2011 56 10620 https://doi.org/10.1007/s10620-011-1794-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1794-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jespersgaard Cathrine Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Fode Peder Laboratory for Microbial Pathogenesis and Host Susceptibility, Department for Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Dybdahl Marianne Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Vind Ida Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Nielsen Ole Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Csillag Claudio Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Munkholm Pia Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Vainer Ben Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Riis Lene Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Elkjaer Margarita Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Pedersen Natalia Department of Gastroenterology, Medical Section, Herlev Hospital, Herlev, Denmark aut NATIONALLICENCE 700 1- Knudsen Elisabeth Department of Gastroenterology, Glostrup University Hospital, Glostrup, Denmark aut NATIONALLICENCE 700 1- Andersen Paal Laboratory for Microbial Pathogenesis and Host Susceptibility, Department for Microbiological Surveillance and Research, Statens Serum Institut, 5 Artillerivej, 2300, Copenhagen S, Denmark aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/12(2011-12-01), 3517-3524 0163-2116 56:12<3517 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer