NOD2 status and human ileal gene expression

Christina M. Hamm, Melissa A. Reimers, Casey K. McCullough, Elizabeth B. Gorbe, Jianyun Lu, C. Charles Gu, Ellen Li, Brian K. Dieckgraefe, Qingqing Gong, Thaddeus S. Stappenbeck, Christian D. Stone, David W. Dietz, Steven R. Hunt

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background: NOD2 single nucleotide polymorphisms have been associated with increased risk of ileal Crohn's disease (CD). This exploratory study was conducted to compare ileal mucosal gene expression in CD patients with and without NOD2 risk alleles. Methods: Ileal samples were prospectively collected from 18 nonsmoking CD patients not treated with anti-TNF-α biologics and 9 nonsmoking control patients without inflammatory bowel disease undergoing initial resection and genotyped for the 3 major NOD2 risk alleles (Arg702Trp, Gly908Arg, Leu1007fs). Microarray analysis was performed in samples from 4 NOD2R (at least 1 risk allele) CD patients, 4 NOD2NR (no risk alleles) CD patients, and 4 NOD2NR controls. Candidate genes selected by significance analysis of microarrays (SAM) were confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays of all the samples. Results: SAM detected upregulation of 18 genes in affected ileum in NOD2R compared to NOD2NR CD patients, including genes related to lymphocyte activation. SAM also detected altered ileal gene expression in unaffected NOD2NR ileal mucosal CD samples compared to NOD2NR control samples. qRT-PCR conducted on all the samples confirmed that increased CD3D expression in affected samples was associated with NOD2R status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7 expression in unaffected samples was associated with CD, independent of NOD2 status. Conclusions: The results support the concept that NOD2 risk alleles contribute to impaired regulation of inflammation in the ileum. Furthermore, altered ileal gene expression, independent of NOD2 status, is detected in the unaffected proximal margin of resected ileum from CD patients.

Original languageEnglish
Pages (from-to)1649-1657
Number of pages9
JournalInflammatory bowel diseases
Volume16
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Crohn's disease
  • Ileum
  • Microarray
  • NOD2

Fingerprint Dive into the research topics of 'NOD2 status and human ileal gene expression'. Together they form a unique fingerprint.

Cite this