Basic–alimentary tractTUCAN (CARD8) Genetic Variants and Inflammatory Bowel Disease
Section snippets
Study Population
A total of 745 IBD cases (372 with CD and 373 with ulcerative colitis) were recruited from patients attending the John Radcliffe Hospital (Oxford) IBD clinic and were compared with healthy unrelated individuals recruited through the UK blood transfusion service and from healthy individuals attending “well-person” screening clinics with their family physicians in Oxfordshire, England (365 controls).
All case patients were diagnosed as having IBD through standard clinical (abdominal pain, weight
TUCAN Case Control
Ten SNPs across the TUCAN gene were identified and genotyped, and the individual SNP results are summarized in Table 1. A significant association with CD and a SNP that changes a cysteine residue to a stop codon at codon 10 (rs2043211) is observed. The population-attributable risk in this CD population for the risk allele (the common allele encoding the Cysteine residue) is 18.4% (95% confidence interval [CI], 6.2%–30.6%). This odds ratio (OR) was more pronounced when the frequency of carriage
Discussion
We have identified a significant association between an SNP in TUCAN (CARD8) and CD. TUCAN is a protein of 643 amino acids and this SNP changes a cysteine residue to a premature stop codon at codon 10. The gene encoding TUCAN is located beneath a peak of linkage for CD identified in a genome-wide scan.19 TUCAN is expressed in the gastrointestinal epithelium, and functional studies suggest that it is a negative regulator of NF-κB21 and also has a regulatory effect on apoptosis.20 From the SNPs
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2021, Cytokine and Growth Factor ReviewsCitation Excerpt :The CARD8 gene, which is located beneath the IBD6 linkage region on chromosome 19, is highly expressed in monocytes and gut epithelia. McGovern [64] investigated the single nucleotide polymorphism (SNP) of the CARD8 gene and its relationship with IBD in 1,110 participants with this disease (CD = 372, UC = 373, controls = 365). Results revealed a significant association between the loss-of-function SNP (Cys10Stop; rs2043211) in CARD8 and CD.
Advances in our understanding of gout as an auto-inflammatory disease
2020, Seminars in Arthritis and RheumatismCitation Excerpt :Variations in CARD8 are associated with several inflammatory diseases [97]. Particularly the rs2043211 allele associated with increased risk of gout is also associated with increased risk of rheumatoid arthritis (RA) [99–101], inflammatory bowel disease (IBD) (disputed association in Crohn's Disease) [102–106], psoriasis [107] and ankylosing spondylitis (AS) [99]. The variation in functional consequences of rs2043211 may be due to alternative splicing effects on the multiple isoforms of CARD8 [97], rather than a simple functional knockout of CARD8 via introduction of a nonsense (stop) codon at amino acid position 10.
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Supported by the Wellcome Trust, the Medical Research Council (United Kingdom), the International Organisation for the Study of Inflammatory Bowel Disease, the Belmont Trust, CORE, and National Association for Crohn’s and Colitis (NACC).