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-1β 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.
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Suk-Kyun
SK
Yang
Hyeri
H
Kim
Myunghee
M
Hong
Jiyoung
J
Lim
Eunkyoung
E
Choi
Byong Duk
BD
Ye
Soo-Kyung
SK
Park
Kyuyoung
K
Song
D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000235:genetics*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C429018:NOD2 protein, human; D009363:Neoplasm Proteins; D053473:Nod2 Signaling Adaptor Protein