Lay Summary

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

One of the most intriguing questions of modern medicine is to understand the nature of our inter-individual differences, such as predilection to disease. In many cases, genetic differences alone do not account for individual differences in disease. Therefore, more and more interest surrounds the study of epigenetics, which focuses on biological processes that modulate gene expression and consequent changes in the phenotype (such as disease predilection) not directly governed by the genetic code.

Genetically identical twins who do not share the same disease (discordant for the disease) are thought to resemble the best examples for epigenetics to play a substantial role in the development of the specific disease. The discordance rate between identical twins is 50-80% for Crohn’s disease (CD) and more than 80% for ulcerative colitis (UC). Consequently, inflammatory bowel diseases (CD and UC) have been recognized as disorders where epigenetic dysregulation may be an important etiologic factor. However, only a small amount of specific research has been performed in IBD in this respect.

One of the epigenetic processes is DNA methylation (methylation of cytosines within cytosine-phosphodiester-guanosine (CpG) dinucleotides) that can be influenced by environment during early development, leading to corresponding phenotype changes. The fact that IBD is becoming more prevalent with the adoption of the Western lifestyle argues that disturbed DNA methylation may be a key epigenetic factor in these diseases. We are planning to perform a high throughput, whole genomic assessment of DNA methylation in relationship to IBD from human peripheral blood leukocyte (PBL) DNA from patients and monozygotic twins suffering from these diseases. Our preliminary studies with PBL DNA from healthy volunteers are encouraging, and indicate that we will be able to identify epigenetic correlates of IBD from blood, if they exist. Such results will set the basis of our further detailed work in this field and likely enable the near future implementation of specific nutritional recommendations for the prevention of IBD.