Divaris, others confirm genetic link to periodontitis through first genome-wide study

Chapel Hill, N.C. (March 4, 2013) — Dr. Kimon Divaris, research assistant professor in the Department of Pediatric Dentistry at the University of North Carolina at Chapel Hill School of Dentistry, today published findings from a study on the genetics of chronic periodontitis in Human Molecular Genetics. The study, led by Divaris, provides novel insights into the genetic underpinnings of periodontitis including new candidate genes and pathways that may be implicated in the pathogenesis of the disease. 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.

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Chronic periodontitis, according to recent national data, affects nearly half of the adult population in the United States with 47.5% of adults having mild, moderate, or severe periodontitis. The disease entails a host inflammatory response to predominantly commensal oral bacteria that is responsible for the destruction of tooth-supporting tissues. In fact, periodontitis is a major cause of tooth loss among adults. Previous studies have linked periodontitis to diseases such as cardiovascular disease, poor diabetes control, adverse pregnancy outcomes, and others.

The study employed, for the first time, a genome-wide association analysis approach; a methodology that allowed the simultaneous investigation of millions of genetic markers (loci) across the human genome for potential associations with chronic periodontitis among a large sample of approximately 5,000 individuals enrolled in the Atherosclerosis Risk in Communities (ARIC) study, a National Institutes of Health-supported longitudinal study. The investigation highlighted several novel regions of the human genome, genes and pathways that may be associated with increased risk for the development of periodontitis. The study examined interactions between genetic and environmental effects and identified genome-wide significant synergistic effects between genetic factors and smoking. Additional analyses revealed a significant role of nervous system, neurotransmitter, and immune response pathways in the risk for chronic periodontitis.

“These findings confirmed what we long suspected about the heritability of 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% 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 ones; although some evidence pointing toward 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 individuals more susceptible to periodontitis, but also to cardiovascular disease, diabetes, arthritis, and other inflammation-related conditions.”

Divaris continued, “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, as well as the consequences of host-microbiome dysbiosis that characterizes many pathological conditions. 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 conditions, such as cardiovascular disease, diabetes, and arthritis.”

The full manuscript is available on Human Molecular Geneticshere.