June 10, 2010 – TORONTO – An emerging arm of molecular biology is introducing a new interpretation of traditional concepts of human disease, explains
an article published today in Nature.
According to author Dr. Arturas Petronis at the Centre for Addiction and Mental Health (CAMH), the emerging science of epigenetics
is offering new insights at the crossroads of genes and the environment, or nature and nurture. Dr. Petronis is head of the
Krembil Family Epigenetics Laboratory at CAMH and an international expert in the field.
Scientists traditionally assume that disease is caused by either genetic or environmental factors, or a combination of the
two. “It has been generally assumed that in complex disease both genes and environment are involved, but the two groups are
very different entities and the investigation of each requires different approaches and techniques. Now we are describing
at the molecular level how environmental factors may trigger our inherited risk factors for genetically based diseases,” says
Dr. Petronis. This science of the gene regulation that activates disease-causing mechanisms is called epigenetics.
Primary causes of disease
“Until now medical science develops treatments for disease symptoms rather than the primary cause. Identification of such
primary causes – would it be genetic or environmental – is rather slow. The role of epigenetic misregulation might be much
more important than that of DNA mutations or hazardous environment,” he adds.
While the basic concepts of epigenetics – or regulation of genes and genomes – were sketched nearly half a century ago, research
has exploded in the past decade.
Population studies confirm that the environment (including nutrition, pollution, various kinds of stress) plays a role in
many diseases. Meanwhile, geneticists routinely map DNA sequence differences in disease. Both epidemiology and genetics have
yielded these insights, but “We can also see that not all features of human diseases can be explained by problems in DNA sequence
variation or environmental agents,” Dr. Petronis says.
Epigenetics and the puzzle of complex disease
Epigenetics provides a new theoretical framework that addresses the vast complexities, irregularities, and controversies detected
in common human diseases. For instance, epigenetics explains why one identical twin may be affected with cancer or diabetes
although the co-twin is perfectly healthy. “In a case like this, the inherited genes are identical and the environment is
similar. But one twin’s risk factor has been triggered, while the other twin’s risk factor has not been triggered,” says Dr.
Petronis. “Epigenetics can offer testable hypotheses to explain how that happens.”
Epigenetic mechanisms also are helpful in explaining why so many diseases include alternating remission (relative wellness)
and relapse. Bipolar disorder, psoriasis, multiple sclerosis, and rheumatoid arthritis are among diseases that are characterized
by these patterns. “With the concepts of epigenetics we can start to understand how a disease risk factor is alternately switched
on and off,” he explains.
Similarly, in cancer the epigenetic variation across different cells of the same tissue may explain why only some cells of
prostate or breast or some other tissue become malignant while others remain normal.
“During the maturation of sperm and egg cells, epigenetic signatures are reprogrammed, which seems to result in a pretty high
error rate,” Dr. Petronis says. “Such common epigenetic mutations may explain one of the evolutionary mysteries – why rates
of conditions such as autism and schizophrenia are not decreasing, despite the fact that individuals affected with these conditions
have fewer children. Classic evolutionary theory tells us that these conditions should disappear, but this is not happening,”
he says. The rate of schizophrenia remains steady at about 1% of the population, and rates of autism may actually be increasing.
If epigenetic origin of human disease is proven, the idea of “switching off” epigenetic risk factors can largely substitute
the older notion that science could fix a “bad” gene by replacing it, says Dr. Petronis. “The future of epigenetic therapy
offers much more exactitude and safety,” he says. Epigenetics research holds promise in dozens of complex traits and diseases
such as cancers, mental illness, asthma, Parkinson’s disease, diabetes, and multiple sclerosis. “Right now we develop treatments
for a disease based on what we know about the average person, or the population as a whole. But epigenetics will help us to
realize our goal of a truly personalized medicine,” he adds.
The sole-authored perspective article “Epigenetics as a unifying principle in the aetiology of complex traits and diseases”
in Nature explains current methodology in detail. Dr. Petronis’ research has been supported by the Canadian Institutes of Health
Research, the US National Institutes of Health, and the Krembil Foundation.
Media Contact: Michael Torres, Media Relations, CAMH ; 416 595 6015
The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital, as well
as one of the world's leading research centres in the area of addiction and mental health. CAMH combines clinical care, research,
education, policy development and health promotion to help transform the lives of people affected by mental health and addiction
CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization