Genetic signature reveals new way to classify gum disease

Researchers at Columbia University Medical Center (CUMC) have devised a new system for classifying periodontal disease based on the genetic signature of affected tissue, rather than on clinical signs and symptoms. The new classification system, the first of its kind, may allow for earlier detection and more individualized treatment of severe periodontitis, before loss of teeth and supportive bone occurs. The findings were published recently in the online edition of the Journal of Dental Research.
Currently, periodontal disease is classified as either "chronic" or "aggressive," based on clinical signs and symptoms, such as severity of gum swelling and extent of bone loss. "However, there is much overlap between the two classes," said study leader Panos N. Papapanou, DDS, PhD, professor and chair of oral and diagnostic sciences at the College of Dental Medicine at CUMC. "Many patients with severe symptoms can be effectively treated, while others with seemingly less severe infection may continue to lose support around their teeth even after therapy. Basically, we don't know whether a periodontal infection is truly aggressive until severe, irreversible damage has occurred."

Looking for a better way to classify periodontitis, Dr. Papapanou turned to cancer as a model. In recent years, cancer biologists have found that, in some cancers, clues to a tumor's aggressiveness and responsiveness to treatment can be found in its genetic signature. To determine if similar patterns could be found in periodontal disease, the CUMC team performed genome-wide expression analyses of diseased gingival (gum) tissue taken from 120 patients with either chronic or aggressive periodontitis. The test group included both males and females ranging in age from 11 to 76 years.

The researchers found that, based on their gene expression signatures, the patients fell into two distinct clusters. "The clusters did not align with the currently accepted periodontitis classification," said Dr. Papapanou. However, the two clusters did differ with respect to the extent and severity of periodontitis, with significantly more serious disease in Cluster 2. The study also found higher levels of infection by known oral pathogens, as well as a higher percentage of males, in Cluster 2 than in Cluster 1, in keeping with the well-established observation that severe periodontitis is more common in men than in women.

"Our data suggest that molecular profiling of gingival tissues can indeed form the basis for the development of an alternative, pathobiology-based classification of periodontitis that correlates well with the clinical presentation of the disease," said Dr. Papapanou.

The researchers' next goal is to conduct a prospective study to validate the new classification system's ability to predict disease outcome. The team also hopes to find simple surrogate biomarkers for the two clusters, as it would be impractical to perform genome-wide testing on every patient.

The new system could offer huge advantages for classifying people with different types of periodontitis. "If a patient is found to be highly susceptible to severe periodontitis, we would be justified in using aggressive therapies, even though that person may have subclinical disease," said Dr. Papapanou. "Now, we wait years to make this determination, and by then, significant damage to the tooth-supporting structures may have occurred.

Genetic techniques have role in future of dental care

A visit to the dentist could one day require a detailed look at how genes in a patient's body are being switched on or off, as well as examining their pearly whites, according to researchers at the University of Adelaide.

In a new paper published in the Australian Dental Journal, researchers from the University of Adelaide's School of Dentistry have written about the current and future use of the field of epigenetics as it relates to oral health.

Co-author Associate Professor Toby Hughes says epigenetics has much to offer in the future treatment and prevention of dental disease.

"Our genetic code, or DNA, is like an orchestra - it contains all of the elements we need to function - but the epigenetic code is essentially the conductor, telling which instruments to play or stay silent, or how to respond at any given moment," Associate Professor Hughes says.

"This is important because, in the case of oral health, epigenetic factors may help to orchestrate healthy and unhealthy states in our mouths. They respond to the current local environment, such as the type and level of our oral microbes, regulating which of our genes are active. This means we could use them to determine an individual's state of health, or even influence how their genes behave. We can't change the underlying genetic code, but we may be able to change when genes are switched on and off," he says.

Associate Professor Hughes is part of a team of researchers at the University of Adelaide that has been studying the underlying genetic and environmental influences on dental development and oral health.

He says that since the completion of the Human Genome Project in 2007, epigenetics has had an increasing role in biological and medical research.

"Dentistry can also greatly benefit from new research in this area," he says. "It could open up a range of opportunities for diagnosis, treatment and prevention.

"We know that our genome plays a key role in our dental development, and in a range of oral diseases; we know that the oral microbiota also play a key role in the state of our oral health; we now have the potential to develop an epigenetic profile of a patient, and use all three of these factors to provide a more personalized level of care.

"Other potential oral health targets for the study of epigenetics include the inflammation and immune responses that lead to periodontitis, which can cause tooth loss; and the development and progression of oral cancers.

"What's most exciting is the possibility of screening for many of these potential oral health problems from an early age so that we can prevent them or reduce their impact."

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The full paper can be found at the Australian Dental Journal's website.