CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis.
A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.
Rahman
P
P
St. Clare's Mercy Hospital, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1C 5B8. prahman@mun.ca
Bartlett
S
S
Siannis
F
F
Pellett
F J
FJ
Farewell
V T
VT
Peddle
L
L
Schentag
C T
CT
Alderdice
C A
CA
Hamilton
S
S
Khraishi
M
M
Tobin
Y
Y
Hefferton
D
D
Gladman
D D
DD
D000328:Adult; D015535:Arthritis, Psoriatic / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein
D002352:Carrier Proteins; D015236:HLA-C Antigens; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein