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Epigenetics, DNA Methylation Patterns and Periodontal Disease (SZU)

2011년 7월 20일 업데이트: University of North Carolina, Chapel Hill

Host DNA Methylation Patterns in Association With Periodontal Disease : MiRNA Changes in Obesity

The overall goal of this research is (1) to identify changes in gene expression and DNA methylation status in subjects who exhibit advanced chronic periodontal inflammation and (2) to identify microRNAs (miRNAs) and the interactive pathways associated with obesity as a modifier of periodontal infection pathogenesis.

연구 개요

상태

완전한

정황

치주 질환

상세 설명

Aim 1. To determine whether diseased periodontal tissues biopsied from patients with periodontal disease will have altered DNA methylation patterns of selected genes as compared to the DNA methylation status biopsies obtained from adjacent, non-diseased periodontal sites, as well as periodontal biopsy samples obtained from non-diseased, healthy subjects.

Aim 2. To determine the role of tissue DNA Methylation on mRNA expression:

2a. To determine whether alterations in tissue mRNA expression (as determined by quantitative PCR) are associated with an aberrant DNA methylation status of respective gene promoter CpG islands in tissue biopsy samples obtained from diseased and non-diseased tissues from patients with periodontal disease and from non-diseased healthy subjects.
2b. By performing laser capture microdissection of biopsy samples from diseased patients [(epithelium, connective tissue and inflammatory infiltrate)] we seek to determine cellular patterns of mRNA expression and DNA methylation of targeted genes comparing inflamed to non-inflamed sites within diseased patients.
2c. We will perform in vitro studies to analyze whether gingival fibroblasts from patients with periodontal disease will show a differential methylation pattern and whether these cells will display a differential inflammatory response when compared to control fibroblasts isolated from healthy subjects.

Aim 3. The aim of this pilot investigation was to determine if miRNA expression differed in the presence or absence of obesity, comparing gingival biopsies obtained from patients with or without periodontal disease.

3a. To determine whether diseased periodontal tissues biopsied from patients with periodontal disease will influence the level of miRNA expression as compared to the biopsies obtained from non-diseased, healthy subjects.
3b. To determine whether BMI [nonobese subjects BMI <30kg/m2, obese subjects >30kg/m2] will influence the level of miRNA expression in biopsies from diseased periodontal tissues as compared to periodontal biopsy samples obtained from non-diseased, healthy subjects.

Gingival samples, gingival crevicular fluid, saliva and plaque samples will be collected and a periodontal examination will be performed. The periodontal assessment will record pocket depth, clinical attachment level and percent bleeding on probing. Blood pressure, height and weight (Body Mass Index assessment) will be obtained on participants as well.

Tissue gene expression by quantitative PCR and DNA methylation sequence analysis, proteomic analyses of gingival crevicular fluid, Differential Methylation Hybridization and, microRNA expression profile by Human miRNA Microarray and Real-time PCR quantification will all be performed.

연구 유형

관찰

등록 (실제)

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

미국
- North Carolina
  - Chapel Hill, North Carolina, 미국, 27599
    - Center for Oral and Systemic Diseases

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

예

연구 대상 성별

모두

샘플링 방법

확률 샘플

연구 인구

Ninety-eight subjects will be recruited from the Graduate Periodontics Clinic and Dental Faculty Practice at the University of North Carolina School of Dentistry and if needed from the general population. Subjects must present with either chronic periodontitis or periodontal health.

설명

Inclusion Criteria:

Subjects must be adult males or females between the ages of 18 and 65 years (inclusive).
Subjects must be able and willing to follow study procedures and instructions.
Subjects must have read, understood and signed an informed consent form.
Subjects must present with at least 20 teeth in the functional dentition, excluding third molars.
Subjects must be in good general health.
Subjects must present with advanced chronic periodontitis (American Dental Association Class 4) as determined by the investigator or designee during the screening periodontal examination. Such subjects will exhibit periodontal pocketing (>5 mm and Bleeding on Probing) and severe alveolar bone loss. Subjects will be under active care for periodontitis and will be treatment planned for periodontal flap surgery.
Control subjects must present with periodontal health as determined by the investigator or designee during the screening periodontal examination. Such subjects will exhibit no evidence of periodontal pocketing (pockets ≤4mm), and no bleeding on probing at the site of the biopsy. Patients from this group will be treatment planned for routine crown extension procedures for restorative reasons, or be volunteers from the general population meeting the inclusion criteria.
24 subjects from group 2 will be enrolled based on Body Mass Index (BMI). Twelve obese subjects (BMI of 30 or greater) and twelve non-obese subjects (BMI less than 30) will be enrolled. Twelve from the obese and twelve from the non-obese group will be split in half based on periodontal status.
6 periodontal healthy non-obese
6 periodontal healthy obese
6 periodontal diseased non-obese
6 periodontal diseased obese

Exclusion Criteria:

Individuals who have a chronic disease with oral manifestations.
Individuals who exhibit gross oral pathology.
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).
Subjects with clinically significant organ disease including impaired renal function, or any bleeding disorder.
Subjects with active infectious diseases such as hepatitis, HIV or tuberculosis.
Severe unrestored caries, or any condition that is likely to require antibiotic treatment over the trial, including the need for prophylactic antibiotic

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

그룹/코호트 수

코호트 및 개입

그룹/코호트
MicroRNA study Obese group (+ periodontitis group) Non-obese group (+ periodontitis group)
DNA methylation study Periodontitis group Healthy periodontium group

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정	기간
DNA methylation patterns of selected candidate genes 기간: Visit 1	Visit 1

2차 결과 측정

결과 측정	기간
Identification of miRNA species 기간: Visit 1	Visit 1

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

University of North Carolina, Chapel Hill

협력자

National Institute of Dental and Craniofacial Research (NIDCR)

수사관

수석 연구원: Steven Offenbacher, DDS, MS, PhD, University of North Carolina, Chapel Hill

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2007년 10월 1일

기본 완료 (실제)

2011년 2월 1일

연구 완료 (실제)

2011년 2월 1일

연구 등록 날짜

최초 제출

2011년 7월 12일

QC 기준을 충족하는 최초 제출

2011년 7월 20일

처음 게시됨 (추정)

2011년 7월 21일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2011년 7월 21일

QC 기준을 충족하는 마지막 업데이트 제출