Crohn's disease associated CARD15 (NOD2) variants are not involved in the susceptibility to type 1 diabetes.
Three variants in the caspase recruitment domain 15/nucleotide-binding oligomerization domain 2 (CARD15/NOD2) gene have been shown to be associated with Crohn's disease (CD). There is a strong support for shared genetic determinants between various autoimmune and inflammatory diseases. In particular, linkage of type 1 diabetes (T1D) and other autoimmune and inflammatory diseases has been reported on chromosome 16, encompassing the region containing the CARD15 gene. We therefore considered this gene as a good candidate for the T1D locus mapped to this region, and we tested the three CARD15 variants in the susceptibility to T1D in two independent settings: family based association analysis in Scandinavian multiplex families that we previously showed to be linked to this region, and case/control association study in a large cohort of French diabetic patients. We found no evidence for association of these variants with T1D overall, nor in subgroups of patients with or without the major risk genotypes at HLA-DRB1, at insulin (INS), or positive or negative for autoantibodies specific to other autoimmune diseases. Our results do not support a role for CD-associated CARD15 variants in the susceptibility to T1D, and suggest that another gene is responsible for the shared susceptibility between autoimmune and inflammatory diseases mapping to this region.
Ghandil
Pegah
P
Genetics of Infectious and Autoimmune Diseases, INSERM U730, Institut Pasteur, Paris, France.
Chelala
Claude
C
Dubois-Laforgue
Danièle
D
Senée
Valérie
V
Caillat-Zucman
Sophie
S
Kockum
Ingrid
I
Luthman
Holgar
H
Nerup
Jorn
J
Pociot
Flemming
F
Timsit
José
J
Julier
Cécile
C
D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005602:France; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D013548:Sweden; D044465:White People
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein