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| Epigenetics can help explain what causes disease According to author Arturas Petronis, MD, PhD, of Toronto, Ontario’s 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. 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, “but the two groups are very different entities and the investigation of each requires different approaches and techniques,” says Petronis. “Now we are describing at the molecular level how environmental factors may trigger our inherited risk factors for genetically based diseases. “Medical science develops treatments for disease symptoms rather than the primary cause,” he continues. “Identification of such primary causes—[whether] 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.” 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, and 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,” Petronis says. Epigenetics provides a new theoretical framework that addresses the vast complexities, irregularities, and controversies detected in common human diseases. For instance, it explains why one identical twin may be affected with cancer or diabetes although the co-twin is perfectly healthy. Epigenetic mechanisms also are helpful in explaining why so many diseases include alternating remission and relapse, such as bipolar disorder, psoriasis, multiple sclerosis, and rheumatoid arthritis. “With the concepts of epigenetics we can start to understand how a disease risk factor is alternately switched on and off,” Petroni explains. “During the maturation of sperm and egg cells, epigenetic signatures are reprogrammed, which seems to result in a pretty high error rate. 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; the rate of schizophrenia remains steady at about 1 percent 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, Petronis says. “The future of epigenetic therapy offers much more exactitude and safety” and its research holds promise in dozens of complex traits and diseases such as cancers, mental illness, asthma, Parkinson’s disease, diabetes, and multiple sclerosis. |
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