No association of the CARD8 (TUCAN) c.30T>A (p.C10X) variant with Crohn's disease: a study in 3 independent European cohorts.
BACKGROUND
A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211) variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The aim of this study was to analyze the frequency of p.C10X in 3 independent European (IBD) cohorts from Germany, Hungary, and the Netherlands.


METHODS
We included a European IBD cohort of 921 patients and compared the p.C10X genotype frequency to 832 healthy controls. The 3 study populations analyzed were: (1) Germany [CD, n = 317; ulcerative colitis (UC), n = 180], (2) Hungary (CD, n = 149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and to clinical characteristics. Ethnically matched controls were included (German, n = 413; Hungarian, n = 202; Dutch, n = 217).


RESULTS
We observed no significant difference in p.C10X genotype frequency in either patients with CD or patients with UC compared with controls in all 3 cohorts. Conversely to the initial association study, we found a trend toward lower frequencies of the suggestive risk wild type in CD from the Netherlands compared with controls (P = 0.14). We found neither evidence for genetic interactions between p.C10X and NOD2 nor the C10X variant to be associated with a CD or UC phenotype.


CONCLUSIONS
Analyzing 3 independent European IBD cohorts, we found no evidence that the C10X variant in CARD8 confers susceptibility for CD.
Büning
Carsten
C
Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Germany.
Schmidt
Hartmut H-J
HH
Molnár
Tamás
T
Drenth
Joost Ph
JP
Fiedler
Thomas
T
Gentz
Enno
E
Todorov
Theodor
T
Baumgart
Daniel C
DC
Sturm
Andreas
A
Nagy
Ferenc
F
Lonovics
János
J
de Jong
Dirk J
DJ
Landt
Olfert
O
Kage
Andreas
A
Nickel
Renate
R
Büttner
Janine
J
Lochs
Herbert
H
Witt
Heiko
H
D000328:Adult; D000483:Alleles; D017209:Apoptosis; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D016133:Polymerase Chain Reaction; D015995:Prevalence
D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; C429018:NOD2 protein, human; D009363:Neoplasm Proteins; D053473:Nod2 Signaling Adaptor Protein; D004247:DNA