title: Association of higher DEFB4 genomic copy number with Crohn's disease.
abstract: OBJECTIVE
  Human beta-defensin 2 (hBD-2 or DEFB4) is a highly inducible, antimicrobial peptide, which may have an important role in the innate immune response at epithelial surfaces. Genomic copy number of DEFB4 is polymorphic, with most individuals possessing 3-5 copies. Increased DEFB4 copy number is a susceptibility factor for psoriasis, whereas a single study in a Crohn's disease (CD) cohort reported that decreased DEFB4 copy number is associated with colonic inflammation. Here, we analyze association of DEFB4 copy number with CD in a New Zealand case-control cohort of European origin.
  
  
  METHODS
  DEFB4 gene copy number was determined using TaqMan quantitative PCR in 466 CD patients and 329 controls. DNA samples, independently genotyped for DEFB4 copy number by alternative methods, were used to validate the assay.
  
  
  RESULTS
  Increased DEFB4 genomic copy number was seen in CD patients compared with controls. Individuals with >4 copies had a significantly higher risk of developing CD than those with <4 copies (odds ratio 1.54; 95% confidence interval 1.13-2.09, P=5e-05). DEFB4 genomic copy number did not differ by disease location within the CD cohort (P=0.948), nor did analysis of CD patients who had undergone surgery detect association of decreased DEFB4 genomic copy number (<4) in colonic CD compared with ileal CD (P=0.120).
  
  
  CONCLUSIONS
  Our results indicate that elevated DEFB4 copy number is a risk factor for CD (irrespective of intestinal location), and challenge previous data supporting positive association of lower DEFB4 genomic copy number with colonic CD.
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand. robert.bentley@otago.ac.nz
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bentley
authors.forename: John
authors.initials: J
authors.lastname: Pearson
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.forename: Cushla
authors.initials: C
authors.lastname: McKinney
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D009520:New Zealand; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D044465:White People / Q000235:genetics*; D023083:beta-Defensins / Q000235:genetics*
chemical_list: C106641:DEFB4A protein, human; D023083:beta-Defensins