Researchers at Columbia University Mailman School of Public Health and the Columbia University College of Dental Medicine have identified 41 master regulator genes that may cause gum disease, also known as periodontal disease. The study was the first of its kind to employ genome-wide reverse engineering to identify the gene pathways that contribute to periodontitis. Findings of the study, “Identification of Master Regulator Genes in Human Periodontitis,” are published in the Journal of Dental Research.
[Photo: Dr. Ryan T. Demmer]
Identification of the genes represents a vital step toward developing compounds that can be used in targeted, individualized treatment of severe periodontitis, before loss of teeth and supportive bone occurs.
In gene expression studies, investigators find those genes that are most commonly expressed in either healthy or diseased tissue. But such studies cannot identify a causal link between these genes and the disease, and often miss genes that affect a larger number of genetic pathways, which may have a large impact on the disease process.
Investigators Dr. Ryan T. Demmer, assistant professor of epidemiology and Dr. Panos N. Papapanou, professor and chair of oral, diagnostic, and rehabilitation sciences at the College of Dental Medicine, “reverse-engineered” the gene expression data to build a map of the genetic interactions that lead to periodontitis and identify individual genes that appear to have the most influence on the disease. According to the researchers, their approach narrows down the list of potentially interesting regulatory genes involved in periodontitis them to focus on the handful of genes that represent the most important players in the process rather than the whole transcriptome.
To identify the genes, Drs. Papapanou and Demmer partnered with CUMC investigators in Systems Biology at Columbia University Medical Center who had previously developed algorithms to identify regulatory genes that fuel cancer growth. The researchers examined RNA from healthy and diseased gum tissues of 120 patients with periodontitis. They applied one algorithm to study the interactions among the genes and used another algorithm to identify genes that disrupt healthy tissue and drive the disease process.
Many of the genes identified in the current study are implicated in immune and inflammatory pathways, confirming laboratory and clinical observations of the development of periodontal disease.
Identification of the master regulator genes will allow investigators to test compounds that interrupt their action, creating treatments that stop periodontal disease at its source.
The paper is titled, “Identification of Master Regulator Genes in Human Periodontitis.” The study was supported by grants from the National Institutes of Health/National Institute of Dental and Craniofacial Research (DE015649, DE021820, DE024735) and by an unrestricted gift from Colgate-Palmolive Inc.