Common Variants in the NLRP3 Region Contribute to Crohn's Disease Susceptibility

Overview

Journal Nat Genet

Specialty Genetics

Date 2008 Dec 23

PMID 19098911

Citations 246

Authors

Alexandra-Chloe Villani

Mathieu Lemire

Genevieve Fortin

Edouard Louis

Mark S Silverberg

Catherine Collette

Nobuyasu Baba

Cecile Libioulle

Jacques Belaiche

Alain Bitton

Daniel Gaudet

Albert Cohen

Diane Langelier

Paul R Fortin

Joan E Wither

Marika Sarfati

Paul Rutgeerts

John D Rioux

Severine Vermeire

Thomas J Hudson

Denis Franchimont

Affiliations

Soon will be listed here.

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.

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