Incessant bouts of abdominal pain, diarrhea, and fever are classic symptoms of Crohn’s disease (CD), a condition that can be extremely stressful for children and their caretakers. Scientists trying to understand the exact cause for this type of inflammatory bowel disease (IBD) recently discovered a number of epigenetic changes — alterations in the genome in response to environmental factors, in children with CD. The report appears in the official journal of the Crohn's & Colitis Foundation of America (CCFA) journal Inflammatory Bowel Diseases.
The study provides substantial evidence of alterations in the DNA in several regions of the genome in children with CD. According to study author Professor Jack Satsangi of University of Edinburgh, and his colleagues, this research can have great implications in designing interventions for CD, a painful, medically incurable illness that may attack anywhere along the digestive system.
What Are Epigenetic Changes?
Epigenetic changes are heritable changes in the phenotype of an organism. This means that there is no change in the underlying DNA sequence, but certain genes are switched on or off depending on genetic predisposition or environmental factors (lifestyle, age, or disease) or both. These changes in the expression of genes cause disease. Epigenetic changes have been related to prevalent diseases like cancer, rheumatoid arthritis, multiple sclerosis, type 2 diabetes, and obesity and even rare conditions such as Angelman syndrome, a neurogenetic disorder, and Prader-Willi syndrome, a cognitive and behavioral disorder.
Epigenetic Changes In CD
Recent research has suggested a link between the onset of CD and epigenetic changes. To further validate this research, the current study conducted a “genome-wide” study in children who had been newly diagnosed with CD. The study to determine epigenetic changes that influence gene behavior was conducted before any treatment was carried out.
The results showed strong evidence of such changes at 65 different sites across the genome. Nineteen sites showed clustering of epigenetic changes, pointing at genetic pathways that might be relevant to CD development. These genetic patterns were observed even in children who had received treatment for CD, as well as in a group of treated adults.
The changes were observed in two specific gene locations (loci), which contain genes responsible for immune and cellular functions that could contribute to the development of CD. Two diagnostic probes used for these loci predicted with great accuracy which children would develop CD, providing a potentially useful "biomarker" for use as a diagnostic test.
One specific gene location has also been associated in the development of several cancers including colorectal cancer. The same area has a known role in the development of T-cells, a key type of immune cell. Other loci that might possibly play a role in development of CD were also identified, but further research is needed to validate this theory.
This study can offer important advances in the clinical management of CD, a disease which affects 1.4 million American adults and children.
"There are exciting and immediate implications for early clinical translation; the discovery of easily accessible biomarkers in peripheral blood to predict disease susceptibility, progression or response to therapy and the potential for new therapeutic targets,” the authors wrote in a press release.
Source: Adams AT, Kennedy NA, Hansen R, et al. Two-stage Genome-wide Methylation Profiling in Childhood-onset Crohnʼs Disease Implicates Epigenetic Alterations at the VMP1/MIR21 and HLA Loci. Inflammatory Bowel Diseases. 2014.