Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

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

doi:10.1007/s10620-011-1794-8

Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

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

Department of Clinical Medicine

16 Citations (Scopus)

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.

Original language	English
Journal	Digestive Diseases and Sciences
Volume	56
Issue number	12
Pages (from-to)	3517-24
Number of pages	8
ISSN	0163-2116
DOIs	https://doi.org/10.1007/s10620-011-1794-8
Publication status	Published - Dec 2011

Keywords

Alleles
Crohn Disease
DNA Copy Number Variations
Denmark
Gene Dosage
Gene Expression Regulation
Genetic Predisposition to Disease
Humans
Peptides, Cyclic
Prevalence
RNA, Messenger
Real-Time Polymerase Chain Reaction
Risk Factors
alpha-Defensins
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

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10.1007/s10620-011-1794-8

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@article{a422ba0d538341fb9287056b0a1aecc4,

title = "Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients",

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.",

keywords = "Alleles, Crohn Disease, DNA Copy Number Variations, Denmark, Gene Dosage, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Peptides, Cyclic, Prevalence, RNA, Messenger, Real-Time Polymerase Chain Reaction, Risk Factors, alpha-Defensins, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't",

author = "Cathrine Jespersgaard and Peder Fode and Marianne Dybdahl and Ida Vind and Nielsen, {Ole Haagen} and Claudio Csillag and Pia Munkholm and Ben Vainer and Lene Riis and Margarita Elkjaer and Natalia Pedersen and Elisabeth Knudsen and Andersen, {Paal Skytt}",

year = "2011",

month = dec,

doi = "10.1007/s10620-011-1794-8",

language = "English",

volume = "56",

pages = "3517--24",

journal = "Digestive Diseases and Sciences",

issn = "0163-2116",

publisher = "Springer",

number = "12",

}

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 - Alleles

KW - Crohn Disease

KW - DNA Copy Number Variations

KW - Denmark

KW - Gene Dosage

KW - Gene Expression Regulation

KW - Genetic Predisposition to Disease

KW - Humans

KW - Peptides, Cyclic

KW - Prevalence

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Risk Factors

KW - alpha-Defensins

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s10620-011-1794-8

DO - 10.1007/s10620-011-1794-8

M3 - Journal article

C2 - 21701837

SN - 0163-2116

VL - 56

SP - 3517

EP - 3524

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

IS - 12

ER -

Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

Abstract

Keywords

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