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PMID: 19098911 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.

Nature genetics ·Vol. 41 ·No. 1 ·2009-01-00 ·Pages 71-6

Villani AC, Lemire M, Fortin G, Louis E, Silverberg MS, Collette C, Baba N, Libioulle C, Belaiche J, Bitton A, Gaudet D, Cohen A, Langelier D, Fortin PR, Wither JE, Sarfati M, Rutgeerts P, Rioux JD, Vermeire S, Hudson TJ, Franchimont D

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.

MeSH Terms
Base Pairing Carrier Proteins/genetics,metabolism Case-Control Studies Crohn Disease/genetics Gene Expression Regulation Genetic Predisposition to Disease Humans NLR Family, Pyrin Domain-Containing 3 Protein Polymorphism, Single Nucleotide/genetics Reproducibility of Results
Chemicals
Carrier Proteins NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 protein, human
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Villani Alexandra-Chloé
Division of Gastroenterology, McGill University Health Centre, Montreal General Hospital, Montréal, Québec, Canada. [email protected]
Lemire Mathieu
Fortin Geneviève
Louis Edouard
Silverberg Mark S
Collette Catherine
Baba Nobuyasu
Libioulle Cécile
Belaiche Jacques
Bitton Alain
Gaudet Daniel
Cohen Albert
Langelier Diane
Fortin Paul R
Wither Joan E
Sarfati Marika
Rutgeerts Paul
Rioux John D
Vermeire Severine
Hudson Thomas J
Franchimont Denis
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.285
Email
[email protected]
Published
2009-01-00
Epub
2008-00-21
Pages
71-6
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2728932
Subset
IM
Grants
NIDDK NIH HHS · R01 DK064869-06A1 · United States
NIAID NIH HHS · P01 AI065687-030001 · United States
NIDDK NIH HHS · U01 DK062423-07 · United States
NIDDK NIH HHS · DK064869 · United States
NIAID NIH HHS · AI065687 · United States
NIAID NIH HHS · P01 AI065687 · United States
NIDDK NIH HHS · U01 DK062432-08 · United States
NIDDK NIH HHS · U01 DK062423 · United States
NIDDK NIH HHS · DK062432 · United States
NIAID NIH HHS · AI067152 · United States
NIDDK NIH HHS · U01 DK062432 · United States
NIDDK NIH HHS · R01 DK064869 · United States
NIDDK NIH HHS · DK624230 · United States
NIAID NIH HHS · U19 AI067152 · United States
NIAID NIH HHS · U19 AI067152-050006 · United States
Databases
OMIM
605956, 606416
RefSeq
NM_001004492
External Links
PubMed source DOI: 10.1038/ng.285 PMC Full Text View journal details
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