Association of CARD8 with inflammatory bowel disease in Koreans

Caspase recruitment domain (CARD)-containing protein 8 (CARD8) is a potential candidate risk gene for inflammatory bowel disease (IBD) because of its role as a component of the NALP3 inflammasome and as an inhibitor of nuclear factor-kappa B. Previous studies examining the association of a CARD8 single-nucleotide polymorphism (SNP) (rs2043211, p.Cys10X) with IBD yielded mixed results in Caucasians that may result from interaction with NALP3 or NOD2 (nucleotide-binding oligomerization domain 2) variants. To understand the genetic association between CARD8/NALP3 and IBD in Koreans, we investigated seven CARD8, four NALP3 and four NOD2 SNPs in 650 Crohn's disease (CD), 660 ulcerative colitis (UC) patients and 688 controls from the Korean population. rs2043211 of CARD8 showed significant association with UC (P=0.011; odds ratio=1.50, 95% confidence intervals=1.12-2.00, P=0.006 under recessive model). In contrast, an SNP in intron 1, rs1972619, was associated with CD only (P=0.033). None of the NALP3 or NOD2 SNPs was significantly associated with CD or UC in the Korean populations. The stop allele of rs2043211 was associated with higher serum interleukin-1 beta levels only in female patients with UC (P=0.027). Our data suggest that CARD8 variants might have roles in the pathogenesis of CD and UC in Koreans. Journal of Human Genetics (2011) 56, 217-223; doi: 10.1038/jhg.2010.170; published online 20 January 2011