Papers

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

Home > Papers > Common variants in the NLRP3 region contribute to Crohn's disease susceptibility

Nature Genetics, January 2009, Volume 41, Number 1

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

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 (Pcombined ¼ 3.49  109, odds ratio ¼ 1.78, confidence interval ¼ 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-1b production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders1,2. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn’s disease.