Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability.
Various genes may influence intestinal barrier function, including MAGI2, MYO9B, and PARD3, which are associated with celiac disease. Because direct measurement of intestinal permeability is difficult, antibodies against gliadin (AGA) and Baker's yeast (anti-Saccharomyces cerevisiae antibodies [ASCA]) can be used as an indirect test. The objective of this study was to investigate whether intestinal permeability, represented by AGA, was correlated with MAGI2, MYO9B, and PARD3. Analyses were performed in patients with Down syndrome, a population with suspected increased intestinal permeability. Correlations between AGA and ASCA were investigated. Patients with Down syndrome (n = 126) were genotyped for six single-nucleotide polymorphisms in MAGI2 (rs1496770, rs6962966, rs9640699), MYO9B (rs1457092, rs2305764), and PARD3 (rs10763976). An allele dosage association of these risk genes and AGA levels was performed. The correlation between AGA and ASCA was studied. A strong correlation was found between AGA and ASCA (p < 0.01). The patient group with one or more risk genotypes had lower mean AGA levels (trend test p = 0.007) and consisted of a larger number of patients with normal AGA levels (p = 9.3 x 10(-5)). Celiac-associated risk genotypes are associated with lower AGA values instead of elevated ones. Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance.
Wolters
Victorien M
VM
Department of Pediatric Gastroenterology, UMC Utrecht, Utrecht, The Netherlands. V.M.Wolters@umcutrecht.nl
Alizadeh
Behrooz Z
BZ
Weijerman
Michel E
ME
Zhernakova
Alexandra
A
van Hoogstraten
Ingrid M W
IM
Mearin
M Luisa
ML
Wapenaar
Martin C
MC
Wijmenga
Cisca
C
Schreurs
Marco W J
MW
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D002446:Celiac Disease / Q000097:blood / Q000235:genetics / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002463:Cell Membrane Permeability / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004314:Down Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005903:Gliadin / Q000276:immunology; D051528:Guanylate Kinases; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009218:Myosins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D029701:Saccharomyces cerevisiae Proteins / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D015415:Biomarkers; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; D029701:Saccharomyces cerevisiae Proteins; C113469:myosin IXB; D005903:Gliadin; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D009218:Myosins