For several centuries the dental profession
has evolved in the recognition and treatment of periodontal disease.
Patients arrive at the dental office, receive a diagnosis of existing
periodontal pathology and, hopefully, complete a course of treatment to
restore as nearly as possible the original state of health. This has
become know as the treatment-based approach to controlling disease.
During the 1920's, Churchill discovered that
individuals in areas with high natural fluoride concentrations in their
drinking water experienced much less decay. Subsequent study
revealed that the fluoride content of enamel constituted a risk factor for
caries. Controlling this risk factor, in this case optimizing
fluoride levels in the drinking water, resulted in large reductions in
decay. This information-based, risk reduction approach to
controlling disease has been termed the "prevention" or "medical"
model. Risk factor control has become commonplace in trying to treat
chronic diseases such as coronary artery disease, osteoporosis, diabetes
and arthritis. Periodontal disease is a chronic disease,
multifactorial in origin. As we become better aware and can identify
those factors which put people at high risk, our periodontal treatment
approaches can be selected with much greater accuracy. Consequently,
we will become more sophisticated at providing the proper level of
preventive services to individuals. Previous editions of the
newsletter have dealt with smoking as one significant risk factor in the
etiology of periodontal disease. Recently, a genetic susceptibility
marker for periodontal disease has been identified which may improve our
ability to decide who must receive extensive periodontal therapy and more
stringent post-treatment preventive services. This newsletter
capsulizes genetic risk assessment in periodontal therapy.
Clinicians have recognized for years that some
individuals get lots of plaque and calculus, but experience little loss of
periodontal support. Other patients seem to have really clean
mouths, but experience extensive bone loss. Their disease is not so
much related to the quantity of bacteria as to some other factor.
While the presence of certain bacteria have been correlated with more
extensive periodontal disease (juvenile periodontitis, localized juvenile
periodontitis), other forms of extensive disease are not so clearly
identified with specific bacteria (like refractory periodontal
disease). Research scientists reason that the spread of disease may
also be dependent on the host response. In 1989, Garrison and
Nichols reported a marked difference between the monocyte cell's response
to bacteria in patients with advanced periodontal destruction and those
who were resistant to disease. In patients with advanced periodontal
disease, blood monocytes (which transform to macrophages once into the
tissues and attack toxins produced by bacteria) were two to three times
more likely to gravitate towards endotoxin produced by gram negative
bacteria than were blood monocytes in those with little disease.
This effect was sustained in spite of the stage of treatment of the
patient's periodontal disease, indicating a genetic response factor was
responsible. And within the past two years, research has indeed
identified a genetic marker that can be correlated with the degree of
tissue destruction that occurs in some periodontal patients with advanced
disease.
Genetic testing for periodontal disease
susceptibility hinges on measuring a gene which regulates the production
of an inflammation mediator called Interleukin 1B. Interleukin 1B is
a strong stimulator of host cells, which destroy bone and soft tissue in
an attempt to limit the spread of infection. This destruction
happens more as a result of the intensity of the response to a bacterial
challenge than to the quantity of bacteria challenging the system.
The intensity of the response is determined by the gene makeup dictating
the quantity of interleukin 1B cells produce in response to a bacterial
challenge. Think of it this way. Each parent contributes
chromosomal material to the gene that determines if interleukin 1B will be
produced in small or large quantities. Each parent can have, from
their parents, a gene makeup which possesses either a negative molecular
base for extra interleukin 1B production or a positive molecular base for
extra interleukin 1B. When parents have a child, the child can then
have three possible combinations of interleukin 1B molecular bases.
They can have negative-negative, negative-positive or positive-positive
combinations. Jotwani, researching gene types, has shown that
positive-positive gene combination individuals produce four times as much
interleukin 1B as do those individuals with a negative-negative
combination. Kornman has calculated periodontal disease progression
to be seven times more likely in positive-positive gene combinations than
in negative-negative combinations. Currently, only smoking overrides
this genetic risk marker as a predictor of periodontal destruction.
This effect on periodontal disease is so pronounced
because interleukin 1B participates in the response to a bacterial
challenge in several ways. Interleukin 1B is one of a class of local
tissue response modifiers called interleukins (older terms taught in
dental schools were cytokines and lymphokines) whose role is to facilitate
cell-to-cell communications. The potentiating effect of Interleukin
1B in bone destruction is enhanced disproportionally in positive-positive
gene combination individuals.
The trade name of this test is PST (for periodontal
sensitivity testing). It requires the clinician to do a finger stick
on the patient and place 3 drops of blood on a sampling card. (A more
recent version allows for saliva samples to be used.) The card is
sent to a commercial laboratory in Flagstaff, Arizona where the genetic
makeup of the interleukin 1B gene site is determined. Currently the
test costs $210.00.
What does a positive test mean in terms of
care? A positive test would first advise the clinician that
supportive therapy at shortened intervals is essential. Perhaps
these patients may need professional deplaquing at four to six week
intervals. It might also indicate a benefit to be gained with the
use of connective tissue stabilizing medications, inflammatory reaction
suppressants and/or periodic antibiotics as well as organism
susceptibility testing. Initial preparation procedures with closer
monitoring may be completed first, but where pockets persist surgical care
followed by stringent maintenance may be the most effective treatment
because it will produce the greatest reduction in Interleukin 1B
production.
This is a new process which will require some time
to become cost effective, but could prove in the near future to be highly
beneficial as a screening tool in predicting disease potential.
Prevention (and perhaps gene manipulation) could then be better tailored
to individual needs. We look forward to any questions you might have
regarding this advance in periodontal
diagnosis.
