Scientists from the University of Iowa and University of Texas South-western Medical Centre, who studied the genetics of two families severely affected by eating disorders, discovered two gene mutations, one in each family, that are associated with increased risk of developing eating disorders.
Moreover, the new study shows that the two genes interact in the same signalling pathway in the brain, and that the two mutations produce the same biological effect. The findings suggest that this pathway might represent a new target for understanding and potentially treating eating disorders.
"If you're considering two randomly discovered genes, the chance that they will interact is small. But, what really sealed the deal for us that the association was real was that the mutations have the same effect," Michael Lutter, M.D., Ph.D., UI assistant professor of psychiatry and senior author of the study said.
Overall, the study suggested that mutations that decrease the activity of a transcription factor- a protein that turns on the expression of other genes- called estrogen-related receptor alpha (ESRRA) increase the risk of eating disorders.
In the new study, 20 members from three generations of one family (10 affected individuals and 10 unaffected), and eight members of a second family (six affected and two unaffected) were analyzed.
The gene discovered in the larger family was ESRRA, a transcription factor that turns on the expression of other genes. The mutation associated with eating disorders decreases ESSRA activity.
The gene found in the second family is a transcriptional repressor called histone deacetylase 4 (HDAC4), which turns off transcription factors, including ESRRA. This mutation is unusual in the sense that it increases the gene's activity -- most mutations decrease or destroy a gene's activity.
Importantly, the team also found that the two affected proteins interacted with one another; HDAC4 binds to ESRRA and inhibits it.
"The fact that the HDAC4 mutation happens to increase the gene activity and happens to increase its ability to repress the ESSRA protein we found in the other family was just beyond coincidence," Lutter says.
The study is published in the Journal of Clinical Investigation.
--ANI (Posted on 09-10-2013)