Scientific Abstract

Proposal No. IBD-0252
Principal Investigator: Richard Kellermayer, M.D., Ph.D.
Applicant Organization: Baylor College of Medicine (Houston, Texas, U.S.A.)
Project Title: Identification of epigenetic correlates in inflammatory bowel diseases from human peripheral blood leukocyte DNA
Period of Award: November 1, 2008 – October 31, 2011

Approximately one million people suffer from inflammatory bowel diseases (IBD) in the United States with 10% of these patients under age 18. The prevalence of the disease has increased in the 20th century along with the adoption of the Western lifestyle. This indicates that environmental and nutritional changes are important etiologic factors in IBD. The high discordance rate of IBD among monozygotic twins further supports the notion that elements independent from genetic constitution influence the development of these disorders. One mode for environmental and nutritional factors to express their effects on living organisms is through the induction of epigenetic changes that include methylation of cytosines within cytosine-phosphodiester-guanosine (CpG) dinucleotides (DNA methylation). In order to address the possibility that such epigenetic changes contribute to the etiology of IBD we will perform genome-wide methylation selective amplification microarrays with peripheral blood leukocyte DNA from individual patients, and also monozygotic twins concordant and discordant for Crohn’s disease (CD) and ulcerative colitis (UC). We expect to identify epigenetic correlates of IBD in the human genome. These high throughput studies will form the basis for further detailed work in this field and may eventually enable the design of specific nutritional interventions for the prevention of IBD.