Causative gene of aggressive periodontitis in young people identified

A research group from Hiroshima University has identified that one of the causative genes for "aggressive periodontitis," which develops in people under 35 years old and progresses rapidly, causing teeth to fall out, is a gene called "MMD2." Aggressive periodontitis includes familial cases, and MMD2 and its mutations were confirmed in patients who developed the disease within the same family. This achievement may lead to screening for aggressive periodontitis and the establishment of early diagnosis and treatment.

There are three types of periodontitis: chronic periodontitis (commonly known as pyorrhea), which mainly develops from middle age onward; periodontitis associated with various genetic diseases; and aggressive periodontitis, which was the subject of this study. In all cases, bacteria in the gums multiply and cause inflammation, dissolving the jawbone that supports the teeth. Aggressive periodontitis can develop as early as the teens, with cases where just eating a banana causes the mouth to become covered in blood. It is characterized by rapid progression, with the affected bone dissolving, making it impossible to support the teeth, which ultimately fall out.

Noriyoshi Mizuno, who studies periodontology at the Graduate School of Biomedical and Health Sciences at Hiroshima University, and his research group, obtained consent from three patients from the same family with aggressive periodontitis and performed whole exome analysis of their DNA to investigate whether there were patient-specific genetic mutations in each protein. From the results, they suspected that a gene called MMD2 was the cause. To obtain more reliable results, they investigated another family in the same manner and found MMD2 mutations, thus identifying MMD2 as the causative gene.

Mizuno and his team initially hypothesized that since the "M" in MMD2 indicates monocytes, it would be strongly expressed in monocytes, a type of immune cell, and proceeded with their research based on this hypothesis. However, they concluded that it is strongly expressed in neutrophils, and that neutrophil abnormalities cause inflammation in periodontal tissues. Compared with neutrophils from healthy individuals, neutrophils from patients showed decreased chemotactic ability to move toward bacteria, making it difficult for them to recognize bacteria as foreign substances.

Next, the researchers investigated whether MMD2 was the cause through animal experiments. When they introduced MMD2 mutations into mice and induced periodontitis, the bone supporting the teeth dissolved, showing symptoms similar to human aggressive periodontitis. Furthermore, when they examined this tissue, few neutrophils had gathered, and many bacteria were confirmed.

Aggressive periodontitis affects 1 in 1000 to 2,000 people, and the Japanese Society of Periodontology defines it as having many patients in their 10s to 30s. While there are cases of familial occurrence, sporadic cases that develop regardless of genetics also exist. Some people need partial dentures in their 20s, making it a disease that causes deep distress for patients, with concerns like "I don't want my friends to find out about my dentures when we go on overnight trips together." If it is detected early, tooth loss can be delayed by performing scaling (tartar removal at dental clinics) as frequently as possible.

Mizuno says that patients he examines in clinical practice sometimes tell him, "Putting myself aside, I'm worried that my child might have this disease, " and "You wouldn't understand the fear of losing teeth one by one." He feels it is "a disease that doesn't cause death but significantly reduces patients' quality of life." Regarding future prospects, he stated: "As the disease progresses, teeth fall out and patients need dentures or implants. Implants are expensive, and there are not yet cases where multiple implants have been placed and observed over the long term. I hope that aggressive periodontitis will become widely known and based on these findings, a genetic testing system will be established that allows early dental intervention."

The research was conducted with funding from the Japan Society for the Promotion of Science's Grants-in-Aid for Scientific Research program and the Japan Agency for Medical Research and Development (AMED)'s Practical Research Project for Rare / Intractable Diseases: "Development of Multi-omics Analysis Using CD45-positive Cells for Improving the Diagnostic Rate of Primary Immunodeficiency" and "Evidence Creation Research Directly Connected to Establishing a Wide-area Diagnostic System for Primary Immunodeficiency Based on Secondary Use of Comprehensive Genome Analysis Data." The results were published in the Journal of Experimental Medicine, an American scientific journal, on July 16.