Genetic association between NLRP3 variants and Crohn's disease does not replicate in a large UK panel
✍ Scribed by Gregory J. Lewis; Dunecan C.O. Massey; Hu Zhang; Francesca Bredin; Mark Tremelling; James C. Lee; Carlo Berzuini; Miles Parkes
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 106 KB
- Volume
- 17
- Category
- Article
- ISSN
- 1078-0998
No coin nor oath required. For personal study only.
✦ Synopsis
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.