Alpha-Defensin DEFA1A3 Gene Copy Number Elevation in Danish Crohn's Disease Patients

作者：Jespersgaard Cathrine; Fode Peder; Dybdahl Marianne; Vind Ida; Nielsen Ole Haagen; Csillag Claudio; Munkholm Pia; Vainer Ben; Riis Lene; Elkjaer Margarita; Pedersen Natalia; Knudsen Elisabeth; Andersen Paal Skytt^*

来源：Digestive Diseases and Sciences, 2011, 56(12): 3517-3524.

DOI：10.1007/s10620-011-1794-8

• Crohn's disease
• Colonic tissue
• Copy number variation
• Defensin
• Genetic association
• Real-time

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.

• 出版日期2011-12