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Updated: Jun 2, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Genetic association between NLRP3 variants and Crohn's disease does not replicate in a large UK panel
Gregory J Lewis1, Dunecan C O Massey, Hu Zhang
1IBD Genetics Research Unit, Department of Gastroenterology, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Background:
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.
Methods:
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.
Results:
No significant associations were found, either on single locus, subphenotype, or haplotype analysis.
Conclusions:
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.
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