Genetic Variation and Gene Expression Levels of Tight Junction Genes Indicates Relationships Between PTEN as well as MAGI1 and Microscopic Colitis

Dig Dis Sci. 2018 Jan;63(1):105-112. doi: 10.1007/s10620-017-4857-7. Epub 2017 Dec 4.


Background and aim: Microscopic colitis (MC) has been associated with increased paracellular permeability. Therefore, we aimed to investigate potential associations between MC and several genes encoding tight junction (TJ) proteins reported to interact with each other.

Methods: The association between MC and single nucleotide polymorphisms (SNP; n = 63) within TJ genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) were investigated in a case-control study (n MC patients = 104 and n controls = 423). The genes that exhibited an association with MC were further investigated for gene expression related to genotype, MC phenotype, and gender using colonic biopsies from MC patients (n = 25) and controls (n = 58).

Results: Based on the number of investigated genes and after correction for multiple testing, an association was detected between a SNP marker in PTEN (rs1234224) and both MC overall (OR = 1.70, 95% CI 1.23-2.34, p = 0.001) and collagenous colitis (CC; OR = 1.79, 95% CI 1.22-2.62, p = 0.003). Further, SNP markers in MAGI1 (rs17417230) and F11R (rs790055) were associated with MC overall (OR = 1.58, 95% CI 1.14-2.19, p = 0.006) and with CC (OR = 2.58, 95% CI 1.27-5.25, p = 0.007), respectively. However, none of the associated SNPs contributed markedly to the expression of the respective genes. Nonetheless, decreased MAGI1 (p = 3.47 × 10-4) and PTEN (p = 0.004) expression was associated with lymphocytic colitis (LC) and CC, respectively, compared to controls.

Conclusions: Decreased expression of PTEN and MAGI1 in the colonic mucosa might contribute to the pathogenesis of MC and its sub-phenotypes. Furthermore, our study indicates that genetic variants of TJ components are predisposing factors in the etiology of MC. Finally, F11R, MAGI1, and PTEN are new candidate genes that exhibit an association with MC.

Keywords: Gene expression; Genetic predisposition; Genotype; Microscopic colitis; Single nucleotide polymorphism; Tight junctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Colitis, Microscopic / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Guanylate Kinases
  • Humans
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • Polymorphism, Single Nucleotide*
  • Tight Junction Proteins / genetics*
  • Tight Junction Proteins / metabolism*
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Tight Junction Proteins
  • Guanylate Kinases
  • MAGI1 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human