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.
調査の概要
状態
完了
条件
詳細な説明
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.
研究の種類
観察的
入学 (実際)
98
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- Center for Oral and Systemic Diseases
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～65年 (大人、高齢者)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
サンプリング方法
確率サンプル
調査対象母集団
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.
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
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MicroRNA study
Obese group (+ periodontitis group) Non-obese group (+ periodontitis group)
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DNA methylation study
Periodontitis group Healthy periodontium group
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
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DNA methylation patterns of selected candidate genes
時間枠：Visit 1
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Visit 1
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二次結果の測定
結果測定 |
時間枠 |
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Identification of miRNA species
時間枠：Visit 1
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Visit 1
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Steven Offenbacher, DDS, MS, PhD、University of North Carolina, Chapel Hill
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2007年10月1日
一次修了 (実際)
2011年2月1日
研究の完了 (実際)
2011年2月1日
試験登録日
最初に提出
2011年7月12日
QC基準を満たした最初の提出物
2011年7月20日
最初の投稿 (見積もり)
2011年7月21日
学習記録の更新
投稿された最後の更新 (見積もり)
2011年7月21日
QC基準を満たした最後の更新が送信されました
2011年7月20日
最終確認日
2011年7月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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