Genetic variation and expression levels of tight junction genes identifies association between MAGI3 and inflammatory bowel disease

Elisabeth Norén,Sven Almer,Jan Söderman

doi:10.1186/s12876-017-0620-y

Elisabeth Norén, Sven Almer + Show 1 more

Open Access

https://doi.org/10.1186/s12876-017-0620-y

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Abstract

BackgroundInflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ). The aim of the study was to investigate single nucleotide polymorphisms (SNP) located in genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD.MethodsAllelic associations between TJ-related genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) and IBD, Crohn’s disease (CD), or ulcerative colitis (UC) were investigated. PTPN22 was included since it’s located in the same genetic region as MAGI3. Gene expression levels were investigated in relation to genotype, inflammatory status, phenotype, and medical treatment.ResultsThe two strongest allelic associations were observed between IBD and SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker (rs6689879) contributed to increased ileal MAGI3 expression level in non-IBD controls. Furthermore, association between inflammation and decreased expression levels of MAGI3, PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased expression of PTPN22 in colonic IBD mucosa, was observed.ConclusionsOur findings lend support to a genetic basis for modulation of intestinal epithelial barrier in IBD, and we have identified MAGI3 as a new candidate gene for IBD.

Highlights

Inflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ)
In conclusion, our findings support a genetic basis for modulation of the intestinal epithelial barrier in IBD, and point to a complex regulation of TJ gene expression through a secondary role of inflammation
By focusing on a Swedish population and a network of interacting TJ components we have identified MAGI3 as a new candidate gene for IBD

Summary

Introduction

Inflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ). The intestinal permeability is further increased in both CD patients and their relatives, indicating underlying hereditary factors [8]. It remains controversial whether this affected permeability is primary, caused by genetic factors, and/or secondary to inflammation or environmental factors. The tight junction (TJ) structure is critical for the permeability properties of the intestine [9] and several studies provide support for a genetic basis in increased permeability [10]

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