Faculty and Staff, Research

Divaris, Others Confirm Genetic Link to Periodontitis through First Genome-wide Study

Dr. Kimon Divaris, research assistant professor in the Department of Pediatric Dentistry, today published findings from the first genome-wide genetic study on chronic periodontitis in Human Molecular Genetics. The study, led by Divaris, confirms the long-standing hypothesis that patients may be genetically predisposed to developing periodontitis. Others involved in the study include the senior author Dr. Steven Offenbacher, Orapharma Distinguished Professor and chair of the UNC School of Dentistry Department of Periodontology; investigators from the UNC Departments of Epidemiology, Medicine, Genetics, Biostatistics and Dental Ecology; and contributors at the University of California-San Francisco, the University of Pittsburgh, and Wake Forest University.

Periodontitis, or the inflammation and gradual breakdown of tooth-supporting tissues, is a leading cause of tooth loss among adults. Previous studies have linked periodontitis to systemic conditions, like cardiovascular disease, poor diabetes control, adverse pregnancy outcomes, and others. Chronic periodontitis, according to recent national data, affects nearly half of the adult population in the U.S. with 47.5 percent of adults having mild, moderate or severe periodontitis.

The study identified, for the first time, several novel regions of the human genome, genes and pathways that may be associated with increased risk for development of periodontitis. Other risk factors, like smoking, also were confirmed to increase one’s likelihood to develop periodontitis, especially when paired with a genetic predisposition.

“These findings confirmed what we long suspected about the heritability of, or genetic predisposition for, chronic periodontitis,” said Divaris. “We found that a considerable proportion of severe periodontitis cases can be explained by common genetic variation, and this proportion exceeds 50 percent when we account for the joint effects of smoking and genetic factors. What was more unexpected and significant was the relationship between the nervous system pathways and periodontitis, complementary to infection and immune response relationships. Although some evidence pointing towards that direction existed, our results were strongly indicative for a role of neurotransmitter and nervous system functions in chronic periodontitis. What is more intriguing is that pathways making up a neurogenic inflammatory reflex may, in part, be responsible for a ’hyper-inflammatory’ trait which could render some people more susceptible to periodontitis, but also to cardiovascular disease, diabetes, arthritis and other inflammation-related conditions.”

The study found that most of the genetic pathways that were associated with the risk of periodontitis were related to nervous system pathways and neurotransmitters. This could mean that the nervous system, while understood to be a part of the inflammation process, may possess genes that signal a person’s individual response to infection.

“We know that intra-oral bacteria that are found on or beneath a person’s gums can result in varying levels of immune response and severity of periodontal disease. These differences in clinical disease are consistent with the existence of a hyper-inflammatory trait, which may contribute to some individuals having aggressive or severe forms of periodontitis when others would have mild forms of the disease,” he explained. “Also, there is some evidence, including findings from our study, implicating nervous system processes in this mechanism.”

Although researchers had long suspected a genetic component of chronic periodontitis, no large-scale genetic investigations at the genome level had been done until now. The study included approximately 5,000 adults who were enrolled in the Atherosclerosis Risk in Communities (ARIC) study, an ongoing longitudinal study of cardiovascular outcomes that is funded by grants from the National Institutes of Health.

Divaris acknowledges there is more work to be done to confirm and benefit from these findings, but feels this study brings us one step closer to really understanding inflammatory diseases such as periodontitis, as well as the dynamic balance between our body’s defense mechanisms and its naturally occurring bacteria (often collectively called the “human microbiome”).

“Although this evidence will require further validation and follow-up experiments, it offers an unprecedented opportunity to unravel previously unknown aspects of the disease pathogenesis. In terms of clinical and public health translation, our findings may serve as a guide for the development of new prevention and treatment approaches. Importantly, understanding the genetic component of chronic periodontitis may provide additional insights about other inflammation-related conditions,” he said.

The full manuscript is available on Human Molecular Genetics here.