Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients.
Dig Dis Sci
; 56(12): 3517-24, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21701837
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
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ARN Mensajero
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Enfermedad de Crohn
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Regulación de la Expresión Génica
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Predisposición Genética a la Enfermedad
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Alfa-Defensinas
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Variaciones en el Número de Copia de ADN
Tipo de estudio:
Etiology_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Dig Dis Sci
Año:
2011
Tipo del documento:
Article
País de afiliación:
Dinamarca