SNP Analysis as a Potential Predictor of Disease Progression Within the UCLA IBD Biobank

Introduction: Inflammatory bowel diseases (IBD) are a set of complex gastrointestinal disorders affecting roughly 3 million Americans. Therapies directed against key mediators have been relatively successful in treating certain aspects of IBD. However, approximately 40% of patients do not initially respond to anti-TNF therapy and an additional 30% of patients lose response over time. Given the high refractory response rates, a more directed and personalized approach to managing these patients is needed. We set out to develop personalized care pathways for IBD based upon predictive biomarkers using samples collected from over 400 patients enrolled in the IBD biobank. Our initial analysis has focused on single nucleotide polymorphisms (SNPs). The aim of the initial research is to determine if two known IBD susceptibility loci, rs3731257 and rs7134599, are predictors of disease progression. Methods: Cohorts within the IBD biobank were identified based on chart review evaluating for inflammation status and disease progression over a fiver year follow up period. Individual SNP's were analyzed using a TaqMan SNP Genotyping Assay. This assay contains two allele-specific TaqMan probes with distinct fluorescent dyes and a PCR primer pairs to detect the two SNP's. Results: A subset analysis of 190 patients showed 96 patients with UC, 85 patients with CD, and 9 patients with indeterminate diagnosis. Within the UC patients, 29 patients had inflammation on initial endoscopy based on pathology reports, while 41 patients were not inflamed. In those with moderate to severe inflammation on initial colonoscopy, 54% had discordant CRP levels while those with no to mild inflammation on colonoscopy had 87% concordant CRP levels. Of the non-inflammed, 46% had disease progression or a flare on follow up and 19 had available colonic biopsy samples on which to perform SNP analyses (10 non-progressors and 9 progressors). For the SNP rs3731257, there was a trend towards significance in that those with GG nucleotides had an increased risk of developing disease progression or clinical flare (OR 6.45, p= 0.14). For the SNP rs7134599, there was no statistical significance. Conclusion: SNP analysis may represent a tool to predict clinical disease progression in those who present with a non-inflamed initial colonoscopy. We hope to continue efforts in characterizing the UCLA IBD biobank to find additional predictive biomarkers through epigenetic and microbial analysis.