Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease

Publication

Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease

Journal Paper/Review - Jun 14, 2005

Török H-P, Brünnler G, Jagiello P, Epplen J T, Griga T, Klein W, Schiemann U, Folwaczny M, Ochsenkühn T, Brand Stephan, Tillack C, Glas J, Tonenchi L, Lohse P, Müller-Myhsok B, Limbersky O, Neugebauer C, Schnitzler F, Seiderer J, Folwaczny C

Citation

Török H, Brünnler G, Jagiello P, Epplen J, Griga T, Klein W, Schiemann U, Folwaczny M, Ochsenkühn T, Brand S, Tillack C, Glas J, Tonenchi L, Lohse P, Müller-Myhsok B, Limbersky O, Neugebauer C, Schnitzler F, Seiderer J, Folwaczny C. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Gut 2005; 54:1421-7.

Type

Journal Paper/Review (English)

Journal

Gut 2005; 54

Publication Date

Jun 14, 2005

Issn Print

0017-5749

Pages

1421-7

Brief description/objective

BACKGROUND AND AIMS
Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions.

PATIENTS AND METHODS
The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed.

RESULTS
No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery.

CONCLUSION
Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.