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.

[1]  S. Chimenti,et al.  Exclusion of CARD15/NOD2 as a candidate susceptibility gene to psoriasis in the Italian population. , 2002, European journal of dermatology : EJD.

[2]  D. Gladman.  Current concepts in psoriatic arthritis. , 2002, Current opinion in rheumatology.

[3]  M. Daly,et al.  CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure. , 2002, American journal of human genetics.

[4]  Judy H. Cho,et al.  Update on genetics of inflammatory bowel disease. , 2002, Current opinion in gastroenterology.

[5]  C. O'Morain,et al.  CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. , 2002, American journal of human genetics.

[6]  James T. Elder,et al.  Lack of association between NOD2 3020InsC frameshift mutation and psoriasis. , 2001, The Journal of investigative dermatology.

[7]  Judy H. Cho,et al.  Update on the genetics of inflammatory bowel disease , 2001, Current gastroenterology reports.

[8]  G. Thomas,et al.  CARD15 mutations in Blau syndrome , 2001, Nature Genetics.

[9]  D. Nicolae,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

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

[11]  D. Gladman,et al.  HLA-C locus alleles in patients with psoriatic arthritis (PsA). , 1999, Human immunology.

[12]  James T. Elder,et al.  Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. , 1997, Human molecular genetics.

[13]  C. Enerbäck,et al.  Evidence that HLA-Cw6 determines early onset of psoriasis, obtained using sequence-specific primers (PCR-SSP). , 1997, Acta dermato-venereologica.

[14]  M. Goodfield.  Skin lesions in psoriasis. , 1994, Bailliere's clinical rheumatology.

[15]  F. I. Lee,et al.  Increased occurrence of psoriasis in patients with Crohn's disease and their relatives. , 1990, The American journal of gastroenterology.

[16]  J. M. Optiz,et al.  Inbreeding in outport Newfoundland. , 1988, American journal of medical genetics.

[17]  D. Gladman,et al.  Psoriatic arthritis (PSA)--an analysis of 220 patients. , 1987, The Quarterly journal of medicine.

[18]  V. Wright,et al.  Familial occurrence of psoriatic arthritis. , 1973, Annals of the rheumatic diseases.

[19]  D. Gudbjartsson,et al.  A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting. , 2003, American journal of human genetics.

[20]  Richard J. Cook,et al.  Multiplicity Considerations in the Design and Analysis of Clinical Trials , 1996 .

[21]  W. Eyler,et al.  PSORIATIC ARTHRITIS. , 1965, Henry Ford Hospital medical bulletin.

[22]  D.,et al.  Regression Models and Life-Tables , 2022 .