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Epigenetics, DNA Methylation Patterns and Periodontal Disease (SZU)

2011年7月20日更新者：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.

研究概览

地位

完全的

条件

牙周疾病

详细说明

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.

研究类型

观察性的

注册 (实际的)

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

美国
- North Carolina
  - Chapel Hill、North Carolina、美国、27599
    - Center for Oral and Systemic Diseases

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年至 65年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

取样方法

概率样本

研究人群

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.

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

团体/队列数

队列和干预

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

研究衡量的是什么？

主要结果指标

结果测量	大体时间
DNA methylation patterns of selected candidate genes 大体时间：Visit 1	Visit 1

次要结果测量

结果测量	大体时间
Identification of miRNA species 大体时间：Visit 1	Visit 1

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of North Carolina, Chapel Hill

合作者

National Institute of Dental and Craniofacial Research (NIDCR)

调查人员

首席研究员：Steven Offenbacher, DDS, MS, PhD、University of North Carolina, Chapel Hill

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2007年10月1日

初级完成 (实际的)

2011年2月1日

研究完成 (实际的)

2011年2月1日

研究注册日期

首次提交

2011年7月12日

首先提交符合 QC 标准的

2011年7月20日

首次发布 (估计)

2011年7月21日

研究记录更新

最后更新发布 (估计)