Role of IL-37 Genetic Variants in Modulating Innate Immune Response to Periodontal Pathogens

A maximum of 440 subjects will be enrolled in this study with the goal of identifying 31 of
each of the three types of IL-37 genotypes (93 total). Subject participation may include 1 to
9 visits lasting over a period of 6 months. Clinical data and medical history data will be
collected at the screening visit to ascertain eligibility. Saliva collected at screening will
be used to determine genotype. If one of the three targeted genotypes results, these patients
will be assigned to the appropriate genotype group until 31 subjects are in each group at
which point recruitment and screening will stop. There are no plans to share genotype
classification with subjects. All subjects will have saliva and dental plaque collected at
baseline. Twenty four of the 93 subjects (8 from each group) will be selected for gingival
biopsy. These 24 subjects will have GCF samples collected at baseline. All subjects will have
GCF samples collected at visit 3. Enrolled subjects (31 of each type of the three genotypes)
will be recalled up to four additional times spread over twelve weeks for blood collection,
to be used for monocyte isolation and whole blood stimulation. Gingival tissue samples will
be used for immunohistochemistry, laser capture and RNA extraction. Medical histories,
demographics, height and weight, clinical and biological data described above will be
recorded and stored on a secure server located at the University of North Carolina. Each
participant enrolled into the study will have a unique identification number that has been
stripped of any information that could be used by non-study members to identify the subject.

Inclusion Criteria:

- Subjects must have read, understood and signed an informed consent form in English.

- Subjects must be able and willing to follow study procedures and instructions in
English.

- Subjects must be adult Caucasian males or females between the ages of 18 and 65 years
(inclusive).

- Subjects must present with at least 20 teeth in the functional dentition, excluding
third molars.

- Subjects must have at least 3 teeth in each posterior sextant.

Exclusion Criteria:

- Chronic disease with oral manifestations including diabetes mellitus.

- Current smoker or one that has stopped smoking less than 2 years prior to enrollment.

- Gross oral pathology other than the periodontal disease.

- Treatment with antibiotics for any medical or dental condition within 1 month prior to
the screening examination.

- Chronic treatment (i.e., two weeks or more) with any medication known to affect
periodontal status (e.g., phenytoin, calcium antagonists, cyclosporin, coumadin,
non-steroidal anti-inflammatory drugs, aspirin) within one month of the screening
examination.

- Ongoing medications initiated less than three months prior to enrollment (i.e.,
medications for chronic medical conditions must be initiated at least three months
prior to enrollment).

- Significant organ disease including impaired renal function, heart murmur, history of
rheumatic fever or valvular disease, or any bleeding disorder.

- Infectious diseases such as hepatitis, HIV or tuberculosis.

- Anemia or other blood dyscrasias.

- Anticoagulant therapy or drugs, such as heparin or warfarin.

- Severe unrestored caries, or any condition that is likely to require antibiotic
treatment over the trial.

- Pregnant, or expect to become pregnant within the next several months.

- Females of child-bearing capacity must be willing to have pregnancy test to confirm
they are not pregnant.

- Anything that would place the individual at increased risk or preclude the
individual's full compliance with or completion of the study.