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

GJ Lewis, DCO Massey, H Zhang… - Inflammatory Bowel …, 2011 - academic.oup.com
GJ Lewis, DCO Massey, H Zhang, F Bredin, M Tremelling, JC Lee, C Berzuini, M Parkes
Inflammatory Bowel Diseases, 2011academic.oup.com
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 …
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. (Inflamm Bowel Dis 2011;)
Oxford University Press