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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e3182a32b03
Original Basic Science Articles

Functional Polymorphisms in the Regulatory Regions of the VNN1 Gene Are Associated with Susceptibility to Inflammatory Bowel Diseases

Gensollen, Thomas1,2,3; Bourges, Christophe1,2,3; Rihet, Pascal PhD4,5; Rostan, Agathe1,2,3; Millet, Virginie1,2,3; Noguchi, Tetsuro PhD6; Bourdon, Violene PhD6; Sobol, Hagay MD, PhD6; Dubuquoy, Laurent PhD7,8,9,10; Bertin, Benjamin PhD7,8,9,10; Fumery, Maturin MD7,8,9,10; Desreumaux, Pierre MD, PhD7,8,9,10; Colombel, Jean-Frédéric MD, PhD11; Hebuterne, Xavier MD, PhD12,13,14; Hofman, Paul MD, PhD12,13,14; Naquet, Philippe MD, PhD1,2,3; Galland, Franck PhD1,2,3

Supplemental Author Material
Erratum

Erratum

In the article on page 2315, volume 19, issue 11, an author was mistakenly not included in the author listing. Mathias Chamaillard, PhD is a contributing author for this article. Dr. Chamaillard‘s affiliation is Inserm U1019 Centre d'Infection et d'Immunité de Lille, Lille, France.

The order of authors is as follows: Thomas Gensollen, Christophe Bourges, Pascal Rihet, PhD, Agathe Rostan, Virginie Millet, Tetsuro Noguchi, PhD, Violene Bourdon, PhD, Hagay Sobol, MD, PhD, Laurent Dubuquoy, PhD, Benjamin Bertin, PhD, Maturin Fumery, MD, Pierre Desreumaux, MD, PhD, Jean-Frédéric Colombel, MD, PhD, Mathias Chamaillard, PhD, Xavier Hebuterne, MD, PhD, Paul Hofman, MD, PhD, Philippe Naquet, MD, PhD, and Franck Galland, PhD.

Inflammatory Bowel Diseases. 20(8):1457, August 2014.

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Abstract

Background:

Vanin-1 is an epithelial pantetheinase, which regulates intestinal inflammation in mouse. We investigated whether human VNN1 levels could be associated to the susceptibility to inflammatory bowel diseases (IBD) and explored the participation of PPARg to these processes.

Methods:

We studied VNN1 expression in colon biopsies from IBD patients. We investigated polymorphisms in the regulatory regions of the VNN1 gene and examined their genetic association with the disease. Functional relevance of these single-nucleotide polymorphisms (SNPs) was assayed, and we tested PPARg in nuclear complexes associated with specific VNN1 polymorphic sequences. In mouse, we examined Vanin-1 expression in gut and feces during dextran sulfate sodium-induced colitis and assayed the effect of PPARg on Vanin-1 regulation.

Results:

VNN1 is expressed by enterocytes and is upregulated in IBD. Three SNPs are statistically associated to IBD. The regions containing these SNPs specifically bind nuclear complexes and are correlated with the VNN1 transcript abundance in colon in an allele-dependent manner. One rare SNP is associated to severe ulcerative colitis with strong VNN1 and dropped PPARg levels. PPARg is involved in nuclear complexes that bound to VNN1 regulatory sites. Similarly, Vanin-1 is tightly regulated in the mouse gut in normal and colitis conditions and PPARg regulates its expression.

Conclusions:

VNN1 is a marker for IBD. Polymorphic positions in the VNN1 locus are direct targets for nuclear factors that might regulate the level of VNN1 in colon, and this could be linked to IBD susceptibility. It is hoped that modulating locally VNN1 expression or activity can be exploited to develop future therapeutic strategies against IBD.

Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

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