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.
|
Authors | 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 |
Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 56
Issue 12
Pg. 3517-24
(Dec 2011)
ISSN: 1573-2568 [Electronic] United States |
PMID | 21701837
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- DEFA1A3 protein, human
- Peptides, Cyclic
- RNA, Messenger
- alpha-Defensins
|
Topics |
- Alleles
- Crohn Disease
(blood, epidemiology, genetics)
- DNA Copy Number Variations
- Denmark
(epidemiology)
- Gene Dosage
- Gene Expression Regulation
- Genetic Predisposition to Disease
- Humans
- Peptides, Cyclic
(biosynthesis, genetics)
- Prevalence
- RNA, Messenger
(genetics)
- Real-Time Polymerase Chain Reaction
- Risk Factors
- alpha-Defensins
(biosynthesis, genetics)
|