Genomic Approach to Find Female-Specific Mechanisms of GWI Pathobiology
Abstract
Gulf War Illness (GWI) is a debilitating condition that is associated with a variety of symptoms including fatigue, headache, memory problems, muscle and joint pain, gastrointestinal issues, neurological problems, hormonal imbalance, and immune dysfunction. The condition appears to affect both men and women who were deployed to the Gulf War, with up to one-third of these affected Veterans remaining ill today. Currently, little is known about what causes the onset and progression of the disease. Diagnosis is made based on a process of elimination, and treatment involves symptom management, rather than targeting the underlying causes of the disease. While little is known about the inner workings of GWI, recent data have suggested that the condition is likely caused by a combination of factors including an individual’s genomic makeup and environmental exposures, such as toxic chemicals and/or pathogens. Further exacerbation or chronic stress exposure during and after wartime may also contribute to aggravation and persistence of GWI. Although men with GWI have been extensively studied, we know much less about women Veterans with GWI due to the very limited numbers of female Veterans studied so far. The few studies assessing gender differences have revealed that women respond to the various stressors in a different way than men. For example, sex hormones influence the responses of the immune and blood pressure systems. The goal of our research efforts is to identify novel, female-specific, genomic characteristics of the development of GWI. This will facilitate a better understanding of the causes of disease. Identification of female-specific disease targets will lead to a better design of therapeutic intervention. Specifically, our more detailed understanding of the dysfunction involved in women with GWI would greatly speed up the identification of promising female-specific biomarkers to improve diagnosis and treatment, which will consider gender differences. There are three components to our research efforts: (1) identification of the genes, involved in the development of GWI in female patients, (2) uncovering the mechanisms, which regulate gene expression response to GWI in female patients, and (3) comparing results of this proposed study with the results of the funded ongoing study in men with GWI. In an effort to understand what is occurring on a genomic level, we aim to understand the changes that occur in activation/deactivation RNA as well as in DNA in females with GWI as compared to their healthy counterparts exposed to similar wartime stressors. This will provide us with a better understanding of how changes in an individual’s genomic makeup cause them to develop the illness versus those who remain healthy today. While it is important to know what specific genes change their expression in the onset and progression of GWI, it is equally important to understand why these genes change their expression. Therefore, on a level of DNA, we want to understand how the changes in the DNA structure (specifically, methylation of DNA) can lead to the onset and progression of GWI as well as potentially alter specific mechanisms that are vital for cell survival, function, and immune defense. We will also evaluate possible changes in the numbers of copies of various genes in the female patients with GWI. We will compare these differences with the differences in the male patients with GWI. Our studies will contribute to the elucidation of differential mechanistic pathways that occur in GWI and their correlation to gender differences in cellular activity, immune, and other systems. One of the most compelling aspects of this proposed research study is our ability to work closely and share our data with the previously Department of Defense (DoD)-funded GWI consortium (W81XWH-13-2-0085, Dr. M. Morris, Principal Investigator [PI], Drs. N. Klimas and T. Craddock, Co-PIs). Another advantage is we do not need to recrui
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710640
Entities
People
- Lubov Nathanson
Organizations
- Nova Southeastern University
- United States Army