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- Title
Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease.
- Authors
Roberts, R. L.; Topless, R. K. G.; Phipps-Green, A. J.; Gearry, R. B.; Barclay, M. L.; Merriman, T. R.
- Abstract
The location of CARD8 within an inflammatory bowel disease (IBD) locus and its role in the NALP3 inflammasome and as a nuclear factor (NF)κB inhibitor make it an attractive candidate risk gene for IBD. However, studies testing for the association of the CARD8 loss-of-function single-nucleotide polymorphism (SNP) rs2043211 with IBD have yielded mixed results. A recent study provided evidence that this discordance may result from an interaction of rs2043211 with loss-of-function variants in nucleotide-binding oligomerization domain protein 2 (NOD2) and a gain-of-function SNP (rs35829419) in NALP3. To confirm this interaction, we conducted a replication in an independent IBD sample set (n=1009 patients, n=517 controls). We found that the presence of the minor allele of rs2043211 with the major allele of rs35829419 conferred a protective effect against Crohn's disease (and vice versa), which intensified in the absence of NOD2 mutations (P1,2/1,1=0.009, odds ratio (OR)=0.66, 95% confidence interval (CI) (0.48–0.90); P1,1/1,2=0.015, OR=0.35, 95% CI (0.15–0.82)). We propose that these genotype combinations protect against gut inflammation by preventing the NALP3 inflammasome from producing excessive interleukin-1β.
- Subjects
CROHN'S disease; INFLAMMATORY bowel diseases; GENETIC mutation; DISEASE risk factors; GENETIC polymorphisms
- Publication
Genes & Immunity, 2010, Vol 11, Issue 4, p351
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2010.11