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Genetic association between NLRP3 variants and Crohn's disease does not replicate in a large UK panel


  • Supported by the Wellcome Trust Case Control Consortium and also the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Addenbrooke's Hospital and University of Cambridge School of Clinical Medicine.



NLRP3 (formerly known as CIAS1 or NALP3) encodes a key component of the inflammasome and is a strong candidate gene for Crohn's disease (CD) susceptibility. A recent study reported significant and internally replicated association between CD and six single nucleotide polymorphisms (SNPs) in a regulatory region 5.3 kb downstream of NLRP3. Independent replication is required to verify these findings.


In all, 1298 CD cases and 1244 healthy controls were genotyped for the six SNPs using Taqman. Single locus, haplotype, and subphenotype analyses were conducted using logistic regression-based methods and PLINK, respectively.


No significant associations were found, either on single locus, subphenotype, or haplotype analysis.


Given our high (>90%) power to replicate findings from the index study, our data suggest either a much smaller effect size for the association between NLRP3 and CD susceptibility than previously reported or the possibility of a false-positive result in the index study. Further studies in other populations are required to determine what role, if any, NLRP3 variants play in CD susceptibility. (Inflamm Bowel Dis 2011;)