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CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis

P Rahman1, S Bartlett, F Siannis

  • 1St. Clare's Mercy Hospital, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1C 5B8. prahman@mun.ca

American Journal of Human Genetics
|July 25, 2003
PubMed

Insights

The CARD15 gene, a susceptibility gene for Crohn disease, is also linked to psoriatic arthritis (PsA). This finding suggests CARD15 is a pleiotropic autoimmune gene, offering new insights into PsA pathogenesis.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Psoriatic arthritis (PsA) and Crohn disease share epidemiological links, including increased psoriasis incidence in Crohn patients.
  • A genomewide scan identified a susceptibility locus for PsA at 16q, overlapping with the CARD15 gene locus, a known Crohn disease susceptibility gene.

Purpose of the Study:

  • To investigate the role of CARD15 gene variants in psoriatic arthritis susceptibility.
  • To determine if CARD15 is a common susceptibility gene for both PsA and Crohn disease.

Main Methods:

  • Screening of 187 PsA patients and 136 healthy controls from Newfoundland for three common CARD15 variants (R702W, leu1007fsinsC, G908R).
  • Utilized polymerase chain reaction with allele-specific primers and gel electrophoresis for variant detection.

Main Results:

  • 28.3% of PsA patients carried at least one CARD15 variant, compared to 11.8% of controls (OR 2.97, P=.0005).
  • Specific allele frequencies for R702W, leu1007fsinsC, and G908R were significantly higher in PsA patients than controls.
  • CARD15 association with PsA was independent of HLA-Cw*0602.

Conclusions:

  • CARD15 is a susceptibility gene for psoriatic arthritis.
  • CARD15 is a pleiotropic autoimmune gene, implicated in both Crohn disease and PsA.
  • This study identifies CARD15 as the first non-MHC gene associated with PsA susceptibility.

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