title: Genetic association between NLRP3 variants and Crohn's disease does not replicate in a large UK panel.
abstract: 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.
authors.affiliation: IBD Genetics Research Unit, Department of Gastroenterology, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Lewis
authors.forename: Dunecan C O
authors.initials: DC
authors.lastname: Massey
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.forename: Francesca
authors.initials: F
authors.lastname: Bredin
authors.forename: Mark
authors.initials: M
authors.lastname: Tremelling
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.forename: Carlo
authors.initials: C
authors.lastname: Berzuini
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D006113:United Kingdom
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human