TY - JOUR
T1 - Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients
AU - Jespersgaard, Cathrine
AU - Fode, Peder
AU - Dybdahl, Marianne
AU - Vind, Ida
AU - Nielsen, Ole Haagen
AU - Csillag, Claudio
AU - Munkholm, Pia
AU - Vainer, Ben
AU - Riis, Lene
AU - Elkjaer, Margarita
AU - Pedersen, Natalia
AU - Knudsen, Elisabeth
AU - Andersen, Paal Skytt
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Colonic tissue
KW - Copy number variation
KW - Crohn's disease
KW - Defensin
KW - Genetic association
KW - Real-time PCR
U2 - 10.1007/s10620-011-1794-8
DO - 10.1007/s10620-011-1794-8
M3 - Journal article
C2 - 21701837
AN - SCOPUS:84856137706
SN - 0163-2116
VL - 56
SP - 3517
EP - 3524
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 12
ER -