The study, led by Rolf Bodmer, Ph.D., was published in Proceedings of National Academy of Sciences.
Dr. Bodmer's lab has discovered that in the fruit fly Drosophila, interactions between cardiac nmr genes (TBX20 in humans) and other transcription factors, are involved in regulating cardiac performance, rhythm and heart muscle structure. TBX20, along with other congenital heart disease genes, has been previously shown to be critical to the development of the embryonic heart first in flies and subsequently in mouse models. However, this study is the first indication that nmr/TBX20 also plays a role in adult heart function. These genes are highly conserved from flies to humans and Bodmer's research showed that some human individuals with structural congenital heart abnormalities, as well as problems with heart function, including arrhythmias and heart failure, also exhibited TBX20 mutations.
"These studies demonstrate that Drosophila has potential as a model system for exploring the genetics underlying human heart disease and for identifying new candidate genes that potentially cause heart disease," said Dr. Bodmer.
To make the connection between human and Drosophila heart malfunction, human subjects with structural congenital heart disease, as well as heart muscle dysfunction were examined. In 96 human subjects with clinical evidence of dilated cardiomyopathy (this causes a weakened heart that cannot pump blood efficiently), DNA analysis identified three different variants of the gene TBX20, suggesting TBX20 may be involved in the development of cardiomyopathy. In addition, TBX20 variants were identified in four children with atrial septal defects.
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Furthermore, the study has shown that people who have a "beneficial" genetic form of apoE (so-called APOE2), which is associated with lower risk of Alzheimer's disease, have lower CSF levels of beta-amyloid peptide 42, a molecule implicated in development of Alzheimer's disease plaques. This finding may explain some of the basis for the known protective effects of the APOE2 observed in large population studies.
Dr. Simona Vuletic, Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington School of Medicine, Seattle, commented, "Understanding the associations between these important molecules in the brain of cognitively normal, healthy people will help us develop better strategies not only for diagnosis, but possibly also better prevention and treatment for Alzheimer's disease. This study also provides baseline data and an opportunity to understand how these normal relationships change, leading to the disease."
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