Association of CARD8 with inflammatory bowel disease in Koreans

Abstract

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 (P¼0.011; odds ratio¼1.50, 95% confidence intervals¼1.12-2.00, P¼0.006 under recessive model). In contrast, an SNP in intron 1, rs1972619, was associated with CD only (P¼0.033). 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-1b levels only in female patients with UC (P¼0.027). Our data suggest that CARD8 variants might have roles in the pathogenesis of CD and UC in Koreans.

Protective and Aggravating Effects of Nlrp3 Inflammasome Activation in IBD Models: Influence of Genetic and Environmental Factors

“…Other authors have confirmed a role for Nlrp3 in IBD, but provided evidence that a gain-of-function mutation of Nlrp3 is associated with IBD [17,18] . Finally, two recent publications could not corroborate any genetic association between Nlrp3 and IBD [19,20] .…”

Long-term Prognosis of the Jejunal Involvement of Crohn’s Disease

“…For example, the NOD2 or ATG16L1 variants, which are regarded as firmly established CD susceptibility genes among whites, are not associated with CD in Asian populations, [1][2][3][4][5] whereas the association of the TNFSF15 variants with a CD risk is stronger in Koreans and Japanese than in whites. [6][7][8] Korean CD patients also differ from western patients in that they have a male predominance in sex distribution, 9,10 predominance of ileocolonic disease in the disease location, [9][10][11] and a higher incidence of perianal fistula in disease behavior. 10,11 Therefore, it is possible that the clinical course of CD differs between Asian and western patients.…”

“…[6][7][8] Korean CD patients also differ from western patients in that they have a male predominance in sex distribution, 9,10 predominance of ileocolonic disease in the disease location, [9][10][11] and a higher incidence of perianal fistula in disease behavior. 10,11 Therefore, it is possible that the clinical course of CD differs between Asian and western patients.…”

Innate immunity functional gene polymorphisms and gout susceptibility

“…Ahmad-Nejad et al, 2004;Alvarez-Rodriguez et al, 2011;Brand et al, 2005;Britton et al, 2001;Coenen et al, 2010;Feldmann et al, 2002;Gazouli et al, 2005;Hoffman et al, 2001Hoffman et al, , 2003Neven et al, 2004;Pontillo et al, 2011;Schoultz et al, 2009;Shen et al, 2010;Snelgrove et al, 2007;Villani et al, 2009;Yang et al, 2011)…”