Two-stage candidate gene study of chromosome 3p demonstrates an association between nonsynonymous variants in the MST1R gene and Crohn's disease.

BACKGROUND: Genomewide linkage studies identified chromosome 3p21 as an IBD locus. Genomewide association studies have supported this locus and the Wellcome Trust Case Control Consortium (WTCCC) study narrowed it to a 0.6 Mb region. Our objectives were to perform a 2-stage candidate gene association study of the 3p locus and to identify linkage disequilibrium (LD) between significant single-nucleotide polymorphisms (SNPs) and an Oxfordshire subset (n = 282) of the WTCCC as well as the HapMap SNPs. METHODS: A total of 197 SNPs in 53 genes from the 3p locus were genotyped on the Illumina platform in a screening cohort of 469 Crohn's disease (CD) patients and 461 controls. Significant associations were then genotyped on the iPLEX platform in the original as well as a second cohort of 139 CD patients, 670 ulcerative colitis (UC) patients, and 1131 controls. All cases and controls were Caucasian and from the Oxfordshire region of the UK. RESULTS: An intronic SNP rs1128535 in the TRAIP gene was associated with CD in the screening and validation cohorts (combined [n = 608] P = 0.0004 [corrected 0.002], odds ratio [OR] 0.77, 95% confidence interval [CI], 0.67-0.89]). No association was seen for UC. Epistasis was seen with the common CARD15 mutations (P = 0.00003 [corrected 0.0006], OR 0.48, 95% CI, 0.34-0.68). No LD was demonstrated with the WTCCC SNPs. Strong LD was demonstrated with 2 nonsynonymous HapMap SNPs in the MST1R gene in an adjacent LD block to the peak WTCCC association, suggesting a distinct association signal. CONCLUSIONS: The LD with these functional MST1R variants implicate this gene as having a possible role in CD pathogenesis.

Artificial bowel markers: a novel method for measuring the accuracy of colonoscopy.

PURPOSE: Colonoscopy is the "gold standard" for assessing colonic mucosal abnormalities. An important component of this is complete examination to the cecum. However, the ability to detect abnormalities is equally important and has received less attention. This study was designed to assess the accuracy of detection of artificial bowel markers as surrogates for small polyps. METHODS: Patients were randomly assigned to receive between zero and four of each of two types of marker. Markers used were 5-mmx5-mm pieces of latex-free rubber or 12-mmx1.5-mm metallic bowel clips. These were placed on insertion of the colonoscope. At the limit of the colonoscopy, a second blinded endoscopist performed the extubation. Six endoscopists took part in the study. Data regarding the number, type, and position of the markers on insertion and withdrawal were recorded as were insertion and withdrawal times. RESULTS: A total of 179 markers (85 clips, 94 rubbers) were placed in 44 patients. The cecal intubation rate was 91 percent. Median intubation time was 20 minutes and withdrawal time was 15 minutes; 139 markers (77.7 percent) were detected on withdrawal (clips, 76.5 percent; rubbers, 78.7 percent). There was no correlation between insertion or withdrawal times and marker detection. Detection rates varied between endoscopists (71-87 percent), but there was no correlation with individual cecal intubation rates (P=0.96). Markers placed at flexures were missed more often (P=0.008). CONCLUSIONS: Artificial markers provide a novel method for assessing colonoscopic accuracy. The results obtained with this method are closely concordant with results from other studies. The technique is potentially useful in training, audit, and future research.