title: Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jespersgaard
authors.forename: Peder
authors.initials: P
authors.lastname: Fode
authors.forename: Marianne
authors.initials: M
authors.lastname: Dybdahl
authors.forename: Ida
authors.initials: I
authors.lastname: Vind
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Claudio
authors.initials: C
authors.lastname: Csillag
authors.forename: Pia
authors.initials: P
authors.lastname: Munkholm
authors.forename: Ben
authors.initials: B
authors.lastname: Vainer
authors.forename: Lene
authors.initials: L
authors.lastname: Riis
authors.forename: Margarita
authors.initials: M
authors.lastname: Elkjaer
authors.forename: Natalia
authors.initials: N
authors.lastname: Pedersen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Knudsen
authors.forename: Paal Skytt
authors.initials: PS
authors.lastname: Andersen
mesh_terms: D000483:Alleles; D003424:Crohn Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D056915:DNA Copy Number Variations; D003718:Denmark / Q000453:epidemiology; D018628:Gene Dosage; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000235:genetics*; D015995:Prevalence; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D023084:alpha-Defensins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C429483:DEFA1A3 protein, human; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D023084:alpha-Defensins