1. ¹Department of Immunology, Hospital Universitario Clínico San Carlos, Madrid, Spain
2. ²Department of Digestive Diseases, Hospital Clínico San Carlos, Madrid, Spain
3. ³Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain

Correspondence: Dr E Urcelay, Department of Immunology, Hospital Universitario Clínico San Carlos, Martin Lagos s/n, 28040 Madrid, Spain. E-mail: eurcelay.hcsc@salud.madrid.org

⁴These authors contributed equally to this work.

Received 14 April 2009; Revised 30 June 2009; Accepted 30 June 2009; Published online 6 August 2009.

Abstract

Genome-wide studies highlighted the effect in Crohn's disease (CD) and ulcerative colitis (UC) susceptibility of single nucleotide polymorphisms (SNPs) in 3p21, where BSN (bassoon), MST1 (macrophage stimulating-1) and MST1R (MST1 Receptor) genes map. MST1R expression was significantly downregulated in multiple sclerosis (MS) compared with control brains, resembling findings in the MS mouse model. We pursued to replicate the effect of this locus on inflammatory bowel diseases and to evaluate its contribution to MS risk. Polymorphisms rs9858542, rs2131109 and rs1128535 were analysed by TaqMan assays in Spanish patients (370 CD, 405 UC and 415 MS) and 800 ethnically matched controls. Allele frequencies of these SNPs were significantly different in CD patients compared with controls [rs9858542: P=0.001, Odds ratio (OR)=1.35; rs2131109: P=0.0005, OR=1.37; rs1128535: P=0.007, OR=0.78] and, specifically, in the ileal phenotype [rs9858542: P=0.0004, OR=1.47; rs2131109: P=0.00009, OR=1.52; rs1128535: P=0.02, OR=0.69]. No differences were detected between UC or MS patients and control individuals. The effect of this locus on CD predisposition was replicated, but no influence on UC or MS predisposition could be detected. This susceptibility locus seems to affect mainly to the ileal CD subphenotype, although this point awaits further corroboration in independent cohorts.