Effect of BSN-MST1 locus on inflammatory bowel disease and multiple sclerosis susceptibility

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 ¼ 0.001, Odds ratio (OR) ¼ 1.35; rs2131109: P ¼ 0.0005, OR ¼ 1.37; rs1128535: P ¼ 0.007, OR ¼ 0.78] and, specifically, in the ileal phenotype [rs9858542: P ¼ 0.0004, OR ¼ 1.47; rs2131109: P ¼ 0.00009, OR ¼ 1.52; rs1128535: P ¼ 0.02, OR ¼ 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.

Association analysis of 3p21 with Crohn's disease in a New Zealand population

“…The most significant SNP from the WTCCC GWAS was rs9858542. This SNP was also found to be significant in a study investigating this region in a Spanish population [25]. rs9858542 is also in LD with rs1800668 (r 2 ϭ 0.955 [in CEPH HapMap samples]) in our study.…”

Genome-wide searching of rare genetic variants in WTCCC data

“…Among the 6 moderate association evidence regions, two regions were also reported in the WTCCC (Table 2). The association evidence of BSN (bassoon protein) has been replicated in the Spanish’s population(Marquez et al 2009). …”

Ron receptor tyrosine kinase signaling as a therapeutic target

“…Multiple studies have identified single nucleotide polymorphisms (SNP) in the 3p21 region. Genome wide association studies (GWAS) studies have found an association with multiple SNPs located within the MST1R (Ron) gene and IBD [68, 69], including two SNPs that are predicted to cause amino acid changes (non-synonymous SNP) [69]. Other GWAS studies report an association between HGFL and IBD [69–72].…”