title: Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
abstract: We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (P(combined) = 3.49 x 10(-9), odds ratio = 1.78, confidence interval = 1.47-2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies. In addition, we observed significant associations between SNPs in the associated regions and NLRP3 expression and IL-1beta production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease.
authors.affiliation: Division of Gastroenterology, McGill University Health Centre, Montreal General Hospital, Montréal, Québec, Canada. alexandra-chloe.villani@mail.mcgill.ca
authors.forename: Alexandra-Chloé
authors.initials: AC
authors.lastname: Villani
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.forename: Geneviève
authors.initials: G
authors.lastname: Fortin
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Collette
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Baba
authors.forename: Cécile
authors.initials: C
authors.lastname: Libioulle
authors.forename: Jacques
authors.initials: J
authors.lastname: Belaiche
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Albert
authors.initials: A
authors.lastname: Cohen
authors.forename: Diane
authors.initials: D
authors.lastname: Langelier
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
authors.forename: Joan E
authors.initials: JE
authors.lastname: Wither
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Denis
authors.initials: D
authors.lastname: Franchimont
mesh_terms: D020029:Base Pairing; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human