Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis

Arthritis Rheum. 2005 Nov;52(11):3596-602. doi: 10.1002/art.21393.

Abstract

Objective: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes.

Methods: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls.

Results: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis.

Conclusion: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthritis, Psoriatic / genetics*
  • Arthritis, Psoriatic / pathology
  • Case-Control Studies
  • Child
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein
  • Organic Cation Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Solute Carrier Family 22 Member 5
  • United Kingdom

Substances

  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Organic Cation Transport Proteins
  • SLC22A4 protein, human
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5