Lay Summary

Proposal No. IBD-0125P
Principal Investigator:  Ben-Zion Levi, Ph.D.
Applicant Organization:  Technion - Israel Institute of Technology (Haifa, Israel)
Project Title:  Association between Nramp1 polymorphisms and Crohn’s disease in Israeli Jewish population
Period of Award:  August 1, 2004 - July 31, 2005

Recent studies have identified an association between Crohn's disease and mutations in a gene termed Nramp1.  In humans, the aberrant expression of the Nramp1 gene is linked to a variety of infectious diseases including leprosy, pulmonary tuberculosis, visceral leishmaniasis, meningococcal meningitis and HIV.  It is also linked to autoimmune diseases, such as rheumatoid arthritis and Crohn's disease.  Interestingly, the genetic variations (termed alleles) are not in the gene, but in a functional region adjacent to the gene that is essential for regulating its expression.  This region is termed promoter region.  The promoter acts like a light dimmer.  Its DNA sequence dictates the ability of regulatory proteins that bind to it to initiate the expression of the gene.

We will study the regulatory protein IRF-8, which binds to the promoter of Nramp1 and regulates its expression.  Genetically inherited variations (polymorphism) in the DNA sequence of Nramp1 promoter can affect the binding of IRF-8 and subsequently lead to aberrant expression of Nramp1 resulting in the development of Crohn's disease in these individuals.

This brief research grant will explore the distribution of Nramp1 promoter alleles among a population of Israeli Jewish patients that have Crohn's disease or ulcerative colitis in comparison to healthy donors.  We expect to identify an association between a specific allele of Nramp1 and Crohn's disease.  This study will help individuals with Crohn's disease by improving diagnostics through the identification of new genetic defects associated with the disorder.