The location of CARD8 within an inflammatory bowel disease (IBD) locus and its role in the NALP3 inflammasome and as a nuclear factor (NF)B 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 (P 1,2/1,1 =0.009, odds ratio (OR)0.66, 95% confidence interval (CI) (0.48-0.90); P 1,1/1,2 =0.015, OR0.35, 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. © 2010 Macmillan Publishers Limited All rights reserved.
CITATION STYLE
Roberts, R. L., Topless, R. K. G., Phipps-Green, A. J., Gearry, R. B., Barclay, M. L., & Merriman, T. R. (2010). Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn’s disease. Genes and Immunity, 11(4), 351–356. https://doi.org/10.1038/gene.2010.11
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