| Literature DB >> 19098911 |
Alexandra-Chloé Villani1, Mathieu Lemire, Geneviève Fortin, Edouard Louis, Mark S Silverberg, Catherine Collette, Nobuyasu Baba, Cécile 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 (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.Entities:
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Year: 2008 PMID： 19098911 PMCID： PMC2728932 DOI： 10.1038/ng.285
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330