Association between CARD8 rs2043211 Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD). Methods: Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger’s test. Results: Eight relevant articles with a total of 10 534 IBD patients [6785 Crohn’s disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR) = 1.210, 95% confidence interval (CI) = 1.013–1.445, p = 0.036] and homozygote contrast (OR = 1.212, 95% CI = 1.005–1.461, p = 0.044). Conclusions: Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population.

[1]  K. Geboes,et al.  My approach to Inflammatory Bowel Disease Unclassified (IBDU) and Indeterminate colitis (IC) : The role of the Pathologist , 2017 .

[2]  P. Söderkvist,et al.  Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis , 2013, Scandinavian journal of rheumatology.

[3]  C. Friel,et al.  Colonic Crohn Disease , 2013, Clinics in Colon and Rectal Surgery.

[4]  Paul H Bornemann,et al.  Ulcerative colitis. , 2013, American family physician.

[5]  H. El‐Serag,et al.  Natural History of Pediatric-onset Inflammatory Bowel Disease: A Systematic Review , 2012, Journal of clinical gastroenterology.

[6]  R. Xavier,et al.  Genetics and pathogenesis of inflammatory bowel disease , 2011, Nature.

[7]  B. Ye,et al.  Association of CARD8 with inflammatory bowel disease in Koreans , 2011, Journal of Human Genetics.

[8]  Tariq Ahmad,et al.  Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 , 2011, Nature Genetics.

[9]  J. Halfvarson Genetics in twins with Crohn's disease: Less pronounced than previously believed? , 2011, Inflammatory bowel diseases.

[10]  Tariq Ahmad,et al.  Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci , 2010, Nature Genetics.

[11]  T. Merriman,et al.  Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease , 2010, Genes and Immunity.

[12]  Seamus J. Martin,et al.  Caspase Recruitment Domain-containing Protein 8 (CARD8) Negatively Regulates NOD2-mediated Signaling* , 2010, The Journal of Biological Chemistry.

[13]  Michael Wasnick,et al.  A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease. , 2009, American journal of human genetics.

[14]  B. Müller-Myhsok,et al.  Epistasis Between Toll-Like Receptor-9 Polymorphisms and Variants in NOD2 and IL23R Modulates Susceptibility to Crohn's Disease , 2009, The American Journal of Gastroenterology.

[15]  M. Fredrikson,et al.  Combined Polymorphisms in Genes Encoding the Inflammasome Components NALP3 and CARD8 Confer Susceptibility to Crohn's Disease in Swedish Men , 2009, The American Journal of Gastroenterology.

[16]  Judy H Cho,et al.  Inflammatory bowel disease. , 2009, The New England journal of medicine.

[17]  O. Combarros,et al.  Deficiency of CARD8 Is Associated with Increased Alzheimer’s Disease Risk in Women , 2008, Dementia and Geriatric Cognitive Disorders.

[18]  T. Todorov,et al.  No association of the CARD8 (TUCAN) c.30T>A (p.C10X) variant with Crohn's disease: A study in 3 independent European cohorts , 2008, Inflammatory bowel diseases.

[19]  N. Prescott,et al.  Novel isoforms of the CARD8 (TUCAN) gene evade a nonsense mutation , 2008, European Journal of Human Genetics.

[20]  Alejandro Balsa,et al.  Deficiency of the NF-κB Inhibitor Caspase Activating and Recruitment Domain 8 in Patients with Rheumatoid Arthritis Is Associated with Disease Severity1 , 2007, The Journal of Immunology.

[21]  R. Xavier,et al.  Unravelling the pathogenesis of inflammatory bowel disease , 2007, Nature.

[22]  P. Rutgeerts,et al.  Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease , 2007, Gut.

[23]  S. Fisher,et al.  Combined evidence from three large British Association studies rejects TUCAN/CARD8 as an IBD susceptibility gene. , 2007, Gastroenterology.

[24]  T. Karlsen,et al.  No association between the TUCAN (CARD8) Cys10Stop mutation and inflammatory bowel disease in a large retrospective German and a clinically well-characterized Norwegian sample. , 2007, Gastroenterology.

[25]  J. Ragoussis,et al.  TUCAN (CARD8) genetic variants and inflammatory bowel disease. , 2006, Gastroenterology.

[26]  T. Ohmura,et al.  A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis. , 2005, Cancer research.

[27]  D. Jewell,et al.  Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. , 2005, Human molecular genetics.

[28]  K. Van Steen,et al.  Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis , 2004, Gut.

[29]  F. Martinon,et al.  NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. , 2004, Immunity.

[30]  G. Bouma,et al.  The immunological and genetic basis of inflammatory bowel disease , 2003, Nature Reviews Immunology.

[31]  A. Leonardi,et al.  TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF‐κB activation , 2002, FEBS letters.

[32]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[33]  J. Bertin,et al.  CARD-8 Protein, a New CARD Family Member That Regulates Caspase-1 Activation and Apoptosis* , 2002, The Journal of Biological Chemistry.

[34]  Seamus J. Martin,et al.  CARDINAL, a Novel Caspase Recruitment Domain Protein, Is an Inhibitor of Multiple NF-κB Activation Pathways* , 2001, The Journal of Biological Chemistry.

[35]  A. Godzik,et al.  TUCAN, an Antiapoptotic Caspase-associated Recruitment Domain Family Protein Overexpressed in Cancer* , 2001, The Journal of Biological Chemistry.

[36]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[37]  Judy H. Cho,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

[38]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[39]  R. Pounder,et al.  Genetics versus environment in inflammatory bowel disease: results of a British twin study , 1996, BMJ.

[40]  C. FordAlexander,et al.  ULCERATIVE colitis. , 1997, Journal of the American Medical Association.