The genetics of NOD-like receptors in Crohn's disease

J. R Fraser Cummings, R. M. Cooney, G. Clarke, J. Beckly, A. Geremia, S. Pathan, L. Hancock, C. Guo, L. R. Cardon, D. P. Jewell

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Abstract

The first Crohn's disease (CD) susceptibility gene identified was CARD15, which is a member of the emerging NOD-like receptor (NLR) family. These function as intracellular cystosolic pattern recognition receptors (PRRs) and play a central role in the innate immune response. We studied other members of the NLR family using a gene-wide haplotype tagging approach in a well-characterised collection of 547 CD patients and 465 controls. Four single nucleotide polymorphisms (SNPs) in NLRP3 had P values < 0.05 and are in high linkage disequilibrium (LD) with each other (r 2 > 0.90 for all four SNPs). rs4925648 and rs10925019 were the most strongly associated with CD susceptibility (P = 0.001, odds ratio (OR) 1.62, 95% CI 1.2-2.18; and P = 6.5 × 10 -4, OR 1.65, 95% CI 1.23-2.19, respectively). rs1363758 located in NLRP11 was associated with CD susceptibility [P = 0.002 (1.64, 1.19-2.25)], which was weakly confirmed in an independent case-cohort collection on joint analysis [P = 0.05, (1.28, 1-1.64)]. On sub-phenotype analysis, an interesting association between NLRP1 and skin extra-intestinal manifestations and colonic, inflammatory CD was identified. None of these results was replicated in the Wellcome Trust Case Control Consortium study and therefore need replication in a further large cohort.

Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalTissue Antigens
Volume76
Issue number1
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

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Keywords

  • Crohn's disease
  • Genetics
  • NOD-like receptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Genetics

Cite this

Cummings, J. R. F., Cooney, R. M., Clarke, G., Beckly, J., Geremia, A., Pathan, S., Hancock, L., Guo, C., Cardon, L. R., & Jewell, D. P. (2010). The genetics of NOD-like receptors in Crohn's disease. Tissue Antigens, 76(1), 48-56. https://doi.org/10.1111/j.1399-0039.2010.01470.x