Association of higher DEFB4 genomic copy number with Crohn's disease.
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.
Bentley
Robert W
RW
Department of Pathology, University of Otago, Christchurch, New Zealand. robert.bentley@otago.ac.nz
Pearson
John
J
Gearry
Richard B
RB
Barclay
Murray L
ML
McKinney
Cushla
C
Merriman
Tony R
TR
Roberts
Rebecca L
RL
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*
C106641:DEFB4A protein, human; D023083:beta-Defensins