title: MAGI2 genetic variation and inflammatory bowel disease.
abstract: BACKGROUND
  Despite recent advances the majority of inflammatory bowel disease (IBD) susceptibility 'genes' remain undiscovered. Recent data suggest that autoimmune conditions may 'share' susceptibility loci. Epidemiological evidence indicates an association between celiac disease and IBD and both conditions demonstrate increased gut permeability. MAGI2, recently implicated in ulcerative colitis (UC) and celiac disease, encodes a scaffolding protein involved in epithelial integrity. Our aim was to test MAGI2 variants for association with IBD and also their role in determining intermediate hereditary phenotypes defined by antibody production to microbial antigens.
  
  
  METHODS
  We genotyped 113 MAGI2 single nucleotide polymorphisms (SNPs) in 681 cases of Crohn's disease (CD), 259 UC cases, and 195 controls.
  
  
  RESULTS
  The most significant IBD association was in intron 6 (rs2160322, P = 0.009) and both UC (P = 0.006) and CD (P = 0.03) contributed to this association. The most significant CD association was with an intron 2 haplotype (rs7785088/rs323149/rs13246026, P = 0.002). We observed highly significant associations with UC in intron 6 (rs7803276/rs7803705, P = 0.002) and also significant associations in introns 2, 6, and 20. Significant associations were seen with: immunoglobulin G (IgG) anti-Saccharomyces cerevisiae antibodies (ASCA)-positive CD in intron 3 (P = 0.003), intron 6 (P = 0.003), and intron 20 (P = 0.001); anti-CBir1-positive CD in intron 3 (P = 0.0001) and intron 6 (P = 0.008); and anti-outer membrane porin C (OmpC)-positive CD in intron 3 (P = 0.0009), and intron 9 (P = 0.007). Quantitative antibody levels were also associated with variants in intron 4 (anti-IgA ASCA, P = 0.0003 and anti-IgG ASCA, P = 0.0002).
  
  
  CONCLUSIONS
  These findings support the significance of the epithelial barrier in IBD pathogenesis.
authors: Medical Genetics Institute & Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. mcgovernd@cshs.org
authors: Dermot P B
authors: DP
authors: McGovern
authors: Kent D
authors: KD
authors: Taylor
authors: Carol
authors: C
authors: Landers
authors: Carrie
authors: C
authors: Derkowski
authors: Deb
authors: D
authors: Dutridge
authors: Marla
authors: M
authors: Dubinsky
authors: Andy
authors: A
authors: Ippoliti
authors: Eric
authors: E
authors: Vasiliauskas
authors: Ling
authors: L
authors: Mei
authors: Emebet
authors: E
authors: Mengesha
authors: Lily
authors: L
authors: King
authors: Sheila
authors: S
authors: Pressman
authors: Stephan R
authors: SR
authors: Targan
authors: Jerome I
authors: JI
authors: Rotter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000907:Antibodies, Bacterial / Q000097:blood; D000908:Antibodies, Fungal / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D051528:Guanylate Kinases; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018272:Porins / Q000276:immunology; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; D015415:Biomarkers; D002352:Carrier Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018272:Porins; D011506:Proteins; D051528:Guanylate Kinases; C485777:MAGI2 protein, human