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Runt‐related transcription factor 3 is associated with ulcerative colitis and shows epistasis with solute carrier family 22, members 4 and 5
Background: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are intestinal inflammatory disorders with a complex genetic background. Mice deficient for the runt‐domain‐transcription‐factor3 (Runx3) develop spontaneous colitis. Human RUNX3 resides i...
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Published in: | Inflammatory bowel diseases 2008-12, Vol.14 (12), p.1615-1622 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
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Online Access: | Get full text |
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Summary: | Background: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are intestinal inflammatory disorders with a complex genetic background. Mice deficient for the runt‐domain‐transcription‐factor3 (Runx3) develop spontaneous colitis. Human RUNX3 resides in an IBD‐susceptibility locus. We studied the association of RUNX3 in a cohort of IBD patients and analyzed the interaction with SLC22A4/5. RUNX3 and OCTN1 mRNA expression was assessed in inflamed and noninflamed mucosa from patients and controls.
Methods: 543 IBD patients (309 CD / 234 UC) and 296 controls were included. Four single nucleotide polymorphisms (SNPs) and 4 microsatellite markers were studied for RUNX3. Five SNPs (including SNP‐207G→C and SNP1672C→T) were analyzed for SLC22A4/5. RUNX3, and OCTN1 expression in mucosal tissue from 30 patients (14 UC / 16 CD) and 6 controls were determined by quantitative polymerase chain reaction.
Results: A significant association between RUNX3‐SNP rs2236851 and UC (OR 1.61; 95% confidence interval [CI] 1.11–2.32, P = 0.020) was found. Carriership is associated with pancolitis (odds ratio [OR] 1.86; 95% CI 1.08–3.21). SLC22A4/5‐SNPs rs272893 and rs273900 are associated with CD (OR 2.16; 95% CI 1.21–3.59 and OR 2.40; 95% CI 1.43–4.05). We found epistasis for carriership of a risk‐associated allele in RUNX3 and SLC22A4/5 for UC patients versus CD patients (OR 3.83; 95% CI 1.26–11.67). RUNX3 mRNA expression is increased (P = 0.01) in inflamed colonic mucosa of UC patients compared to noninflamed mucosa and controls.
Conclusions: We provide evidence for the genetic association of RUNX3 with UC and for CD with the IBD5 locus including SLC22A4/5. An epistatic effect of RUNX3 and SLC22A4 was associated with an increased risk for UC. Our data suggest a role for RUNX3 in UC susceptibility.
(Inflamm Bowel Dis 2008) |
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ISSN: | 1078-0998 1536-4844 |
DOI: | 10.1002/ibd.20610 |