Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-17
pubmed:abstractText
Reduced expression of Paneth cell antimicrobial alpha-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5' flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell alpha-defensins is a primary factor in disease pathogenesis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-10485457, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-11352068, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-11709511, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-12167685, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-12408869, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15194649, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15479689, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15591523, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15618294, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15692051, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15778706, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15790844, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15833914, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-15861209, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16083717, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16151544, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16330776, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16391570, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16415884, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16493449, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16534846, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16909382, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16931742, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-16989824, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-17554300, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-17709525, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-17965060, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-18192283, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-18258845, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-18457593, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-18849966, http://linkedlifedata.com/resource/pubmed/commentcorrection/19221600-9697701
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1932-6203
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e4496
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
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