Periodontal disease - Istenhegyi Centre for Genetic Diagnostics

The role of periodontopathogenic bacteria and genetic predisposition in the development of periodontal diseases

Periodontopathogenic bacteria (e.g. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Treponema denticola) have already been identified as factors contributing to the development of periodontitis. Other risk factors include smoking and poor oral hygiene. Dentists, however, often see patients with progressive periodontal diseases in spite of their low bacterium level, good oral hygiene and regular checkups. Studies show that the progression of periodontitis cannot always be explained by bacteria and other environmental and anatomical factors alone. Based on these findings, the role of genetic factors came into consideration.

Our immune system produces cytokins to eliminate periodontopathogenic bacteria, so it is not surprising that there is a link between the concentration of local inflammation mediators (TNF-?, interleukins) and the severity of the disease. Compared with healthy individuals, patients with periodontitis have a higher level of the protein interleukin-1? (IL-1?). The IL-1 gene plays a role in several destructive mechanisms that lead to periodontitis, including bone absorption. This explains how a higher IL-1 protein level of the gingival tissue, triggered by bacteria, results in severe inflammatory reaction and the aggressive destruction of the bone and the soft tissues.

The phenomenon was linked to a specific variant of the IL-1 gene family. People with this genotype have a higher predisposition for periodontal bleeding and a 2.7-times increase in the risk of tooth loss. If the patient is a heavy smoker, this risk is 7.7 times higher. Other traditional clinical parameters for the prediction of the prognosis did not show a significant effect.

Around 300 bacteria have been identified in the human mouth. Deep periodontal pockets are ideal hosts for bacteria. Instead of saliva, the pockets are filled with a stagnating liquid and the lack of oxygen, which increases with the depth of the sulcus (pocket) and provides ideal conditions for the breeding of anaerobic bacteria. A healthy sulcus is dominated by aerobic bacteria (Streptococcus mitis, S. sanguis, Lactobacillae, Neisseriaceae, Actinomyces species), which are "useful" bacteria, since they do not damage the gums and prevent the settlement of pathogen bacteria. The emergence and progress of periodontitis involves the breeding of anaerobic bacteria. Their metabolites (adhesines, proteases, phosphatases, immune suppressors) not only directly damage the periodontal tissue, but also inactivate the host's immune system.

A healthy sulcus also contains periodontopathogenic bacteria, but in a low concentration. The dominance of these over the friendly bacteria depends on the state of the immune system. An intact immune system is usually able to keep the small number of periodontopathogenic bacteria under control, but if it is damaged, due to stress, medication, hormonal changes or smoking, it is unable to fulfil this role.

Genetic testing for periodontitis

Periodontitis is linked with two genetic variations within the IL-1 gene family. (Kornman et al., 1997; Gore et al., 1998). The aim of genetic testing is to genotype these variations, namely interleukin (IL)-1A gene at position -889 and IL-1B gene at position +3953. In both positions, allele-1 represents cytidine C and allele-2 represents thymidine (T).

Bacterium testing for periodontitis

Bacteria causing periodontitis are harboured in the deep gingival pockets. They are anaerobic bacteria, which are destroyed in the presence of oxygen, so they are very difficult to culture. Enzymatic testing can be done in the doctor's surgery, but this procedure cannot identify all bacteria and cannot give a species-specific classification. Immunology tests require peripheral blood samples, which usually cannot be obtained in the dentist's surgery.

Molecular genetic testing, however, does not have such disadvantages. We identify the DNA of the pathogens and this procedure does not require the presence of live bacteria or blood sampling. It is species-specific and has a better sensitivity. During the test DNA is isolated from the sample, a specific DNA section is copied through polymerase chain reaction (PCR), and then hybridisation is used to identify these DNA sections.

The detection of the IL-1 genotype, as well as bacteria and other risk factors enable the dentist to determine the patient's periodontal status and the risk of future tooth loss. These data help the prevention of periodontitis, enable the dentist to plan a tailor-made treatment and also reduce costs.

Indications

Indications for genetic testing for periodontitis

Refractory, therapy-resistant periodontitis:
A positive test explains the failure of previous treatments and indicates the need for alternative therapies.
Progressive periodontitis:
A positive test indicates the need for more aggressive therapy and more monitoring.
Early signs of periodontitis:
Prior to treatment, the test enables the dentist to plan a tailor-made therapy, stop the progress of the disease and avoid excessive treatment.
Relatives of patients with a positive genotype:
It emphasises the importance of more intensive prevention for non-symptomatic patients with a positive genotype.
Prior to a costly dental restorative treatment:
Knowing the genotype helps to detect the risk of possible complications after implant and tissue regeneration treatments.
Negative patient attitude:
Patients' willingness to cooperate is shown to improve considerably when they are aware of the genetic risk factors.

Indications for bacterium testing for periodontitis
The majority of chronic gingivitis and low to moderate periodontitis cases can be treated successfully with regular mechanical intervention. In 15-20% of cases, however, pronounced progression can be detected, for example early periodontal diseases appear, such as localised juvenile periodontitis (LJP, marker for Actinobacillus actinomycetemcomitans), rapidly progressive periodontitis (RPP, often with a history of LJP and high bacterium concentration). Bacterium testing is also recommended in the case of severe, therapy-resistant refractory adult periodontitis (AP), inflammation after implants and sulcus formation.

Bacterium testing for periodontitis enables us to:

select the appropriate antibiotic treatment
identify which teeth could be affected
monitor the progress of therapy
detect reinfection at an early stage during check-ups
identify affected relatives and detect the source of reinfection
assess the risks of implantation before costly restorative treatments
improve patient attitude

Our new service: Pre-implantation Genetic Diagnostics (PGD)

PGD is recommended when parents are at risk of transmitting a known genetic condition to their future child that would severely impair the child's prospect or quality of life (=high-risk PGD). PGD is considered in cases of monogenic disorders (autosomal recessive, autosomal dominant or X-linked disorders) or the result of a balanced chromosomal translocation.