Two-stage candidate gene study of chromosome 3p demonstrates an association between nonsynonymous variants in the MST1R gene and Crohn's disease
✍ Scribed by John B. Beckly; Laura Hancock; Alessandra Geremia; J.R. Fraser Cummings; Andrew Morris; Rachel Cooney; Saad Pathan; Changcun Guo; Derek P. Jewell
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 394 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
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.