title: Crohn's disease associated CARD15 (NOD2) variants are not involved in the susceptibility to type 1 diabetes.
abstract: 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.
authors.affiliation: Genetics of Infectious and Autoimmune Diseases, INSERM U730, Institut Pasteur, Paris, France.
authors.forename: Pegah
authors.initials: P
authors.lastname: Ghandil
authors.forename: Claude
authors.initials: C
authors.lastname: Chelala
authors.forename: Danièle
authors.initials: D
authors.lastname: Dubois-Laforgue
authors.forename: Valérie
authors.initials: V
authors.lastname: Senée
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Holgar
authors.initials: H
authors.lastname: Luthman
authors.forename: Jorn
authors.initials: J
authors.lastname: Nerup
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.forename: José
authors.initials: J
authors.lastname: Timsit
authors.forename: Cécile
authors.initials: C
authors.lastname: Julier
mesh_terms: 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
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein