RT Journal Article
SR Electronic
T1 Polymorphisms in the <em>DLG5</em> and OCTN cation transporter genes in Crohn’s disease
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1421
OP 1427
DO 10.1136/gut.2005.066340
VO 54
IS 10
A1 H-P Török
A1 J Glas
A1 L Tonenchi
A1 P Lohse
A1 B Müller-Myhsok
A1 O Limbersky
A1 C Neugebauer
A1 F Schnitzler
A1 J Seiderer
A1 C Tillack
A1 S Brand
A1 G Brünnler
A1 P Jagiello
A1 J T Epplen
A1 T Griga
A1 W Klein
A1 U Schiemann
A1 M Folwaczny
A1 T Ochsenkühn
A1 C Folwaczny
YR 2005
UL http://gut.bmj.com/content/54/10/1421.abstract
AB 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.