Author + information
- Ray E. Hershberger, MD⁎ ()
- ↵⁎Heart Failure and Cardiac Transplantation, Oregon Health and Science University, UHN-62, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239
We appreciate the interest in our recent review (1) of the genetic basis of dilated cardiomyopathy from Drs. Poller, Schultheiss, and Kühl. We agree with the first point that the screening of healthy, unselected populations is always important to more fully understand genetic variation. We also agree with the general premise of the second point that understanding gene/environment interactions can be helpful, and at times essential, for understanding the pathogenesis and progression of genetic disease.
We also suggest that the first point of Drs Poller and colleagues (“ … unless representative healthy populations are screened … ”) may be even more important for their work (2) to ascertain any role of viruses in causing idiopathic dilated cardiomyopathy (IDC). In their study only myocardial samples from patients with IDC were examined for virus, but no myocardial samples from any control group (e.g., ischemic cardiomyopathy, or a “representative healthy population”) were reported. This raises the question of whether viruses, ubiquitous in all living organisms and perhaps equally so in control myocardium, are relevant for IDC.
Although it is likely that environmental influences affect penetrance and phenotype, it is also clear that a great deal of phenotypic variation can be attributed to epigenetic variation independent of environmental influence. Transcriptionally competent retrotransposons likely number in the thousands in mammalian genomes, and, for example, have been shown to cause the considerable phenotypic variation that is routinely observed in isogenic mice strains (3). Understanding the genetic, epigenetic, and environmental factors that cause or modify human disease will require a great deal of careful effort supported by the most robust controls possible.
- American College of Cardiology Foundation
- Burkett E.L.,
- Hershberger R.E.
- Kühl U.,
- Pauschinger M.,
- Noutsias M.,
- et al.