Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis

Aliment Pharmacol Ther. 2006 Feb 15;23(4):497-506. doi: 10.1111/j.1365-2036.2006.02780.x.


Background: Two variants in the organic cation transporter gene cluster have been recently reported to confer susceptibility to Crohn's disease (CD).

Aim: To investigate these variants in CD and ulcerative colitis (UC), and their interaction with CARD15 gene and correlation to clinical subphenotypes.

Methods: Case-control association analysis was performed in 899 patients (444 CD and 455 UC) and 611 controls. The organic cation transporter gene cluster single nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length polymorphic analysis and multiplex pyrosequencing, respectively.

Results: The 1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P = 0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033), respectively. Compared with controls, the TC haplotype frequency was increased in both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15-negative CD, respectively. Similar results were found in UC. In CD a significant association of the TC haplotype was found with presence of perianal fistulae (P = 0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was more frequent in patients with more extensive disease (P = 0.015), and those on immunosuppressives (P = 0.004).

Conclusions: Organic cation transporter gene cluster variants may confer susceptibility to both CD and UC, and the TC haplotype may influence some clinical features of IBD, but does not interact with CARD15 variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Female
  • Gene Frequency / genetics
  • Haplotypes / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Nod2 Signaling Adaptor Protein
  • Organic Cation Transport Proteins / genetics*
  • Organic Cation Transporter 1 / genetics
  • Organic Cation Transporter 2
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics


  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • SLC22A2 protein, human