Association Between IL-1 and IL-1Ra Gene Polymorphisms With Peri-implantitis
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Frequency of Participants with polymorphism in the IL-1 gene cluster
研究概览
简要总结
The primary objective of this study is to evaluate interleukin-1(IL-1) gene group polymorphisms in patients with peri-implantitis and to compare them with patients with peri-implant health (control group), taking into account smoking status, gender, age and history of periodontitis.The aim of this investigation is also to look at the levels of the inflammatory response markers IL-1 beta, prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF alpha) in the peri-implant crevicular fluid of patients with healthy oral implants in comparison with individuals with peri-implantitis, under consideration of the patients´ individual IL-1 genotype.
The main hypothesis is that individuals carrying the polymorphism in the IL-1 gene cluster are susceptible to develop peri-implantitis through altered IL-1 and IL-1 receptor antagonist (IL-1Ra) production. A second hypothesis is that both in healthy individuals and especially pronounced in patients having peri-implantitis, an IL-1-positive genotype will result in higher levels of inflammatory cytokines (IL-1 beta, PGE2 and TNF alpha) than an IL-1- negative genotype.
Patients included in the study will be recruited from the Dental Clinic Egas Moniz implant maintenance program and will only be used for this study. All possible candidates will receive a questionnaire and if the patient's medical history is in accordance with study inclusion criteria, and if they agree to participate, informed consent will be signed. All clinical data will be collected by the same examiner.
Genes IL-1A and IL-1B control the production of the proinflammatory proteins, IL-1 alpha and IL-1 beta, respectively. IL-1RN gene controls the synthesis of the IL-1Ra, which impedes the function of IL-1alpha and IL-1beta by competing for receptor binding. Polymorphisms of the following genes will be analyzed: IL-1A-889, IL-1B + 3954, IL-1B-511 and IL-1 RN from patients with peri-implantitis and peri-implant health. For the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab.
For the biochemical analysis of the inflammatory mediators IL-1 beta, TNF alpha and PGE2 a peri-implant crevicular fluid collection will be performed by inserting paper strips into peri-implant sulcus or pocket, in situations of peri-implantitis from the most affected location, while in situations of peri-implant health from the mesio-buccal location.
详细描述
The study will be conducted according to the principles of the Helsinki Declaration (reviewed in 2013). Appropriate measures will be taken for the protection of patient data. The study was approved by Instituto Universitário Egas Moniz (IUEM) Scientific Council on 3 July 2019 and the approval of the Ethics Committee of Egas Moniz was received on 24 July 2019. Authorization was also obtained by the Clinical Direction of Egas Moniz Dental Clinic to carry out research work at the Clinic of the University.
The study will consist of two groups, the first consisting of patients with peri-implantitis (bleeding and / or suppuration on probing, probing depth (PD) equal or greater than 6mm and bone loss equal to or greater than 3mm) and the second group (control group) formed by patients with peri-implant health (peri implant mucosa without inflammatory signs and absence of peri-implant bone loss). The definition of peri-implantitis and peri-implant health will be in accordance with the new classification of periodontal and peri-implant diseases (American Academy of Periodontology (AAP) and European Federation of Periodontology (EFP) 2017)
A peri-implant probing examination (6 locations with a CP12 graduated periodontal probe) and evaluation of plaque accumulation and gingival indexes (4 locations) will be performed as usual at implant maintenance appointments. The presence of bleeding on probing or pus will also be evaluated. An implant control radiograph will be taken in cases where there is a probing depth more than 6mm. All clinical data will be collected by the same examiner. Prior to the study, a training and calibration exercise will be performed for PD measurements using patients not included in the study.
The periodontal condition of the patients will be also evaluated. To consider periodontal health, patients should have the following clinical characteristics: up to 10% of locations with bleeding on probing, absence of erythema and edema, absence of patient symptoms, absence of clinical attachment loss and bone loss and PD < 3mm (AAP and EFP 2017). A patient is a periodontitis case if: interdental clinical attachment loss is detectable at least 2 non-adjacent teeth, or buccal or oral clinical attachment loss >3mm with pocketing >3mm is detectable at least 2 teeth. The classification of periodontitis will be done on a multi-dimensional staging and grading system.
In the case of a peri-implant health situation, plaque control measures will be taken, while in cases of peri-implantitis the patient will be referred for a specific treatment appointment. In situations of patients with more than one implant affected by peri-implantitis, the one with the greatest bone loss will be chosen for the study.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •patients with Caucasian parents and grandparents
- •patients with dental implants placed at the Dental Clinic Egas Moniz or out
- •patients with peri-implantitis diagnosis
- •implants in function for at least 1 year
- •patients included in a periodontal / peri-implant support program
- •patients who agree to participate in the study and sign informed consent
排除标准
- •patients with any systemic condition that affects the immune system
- •pregnant women
- •patients who have taken chronic antibiotics or anti-inflammatory drugs in the last 6 months
- •patients who have undergone peri-implant treatment in the area to be evaluated
结局指标
主要结局
Frequency of Participants with polymorphism in the IL-1 gene cluster
时间窗: 1 month after sample collection
In the IL-1A-889 gene, two possible alleles are expected to be found, allele 1 (83 base pairs (bp) + 16 bp), allele 2 - allele with nucleotide sequence changed (99 bp). In the IL-1B + 3954 gene, two possible alleles are expected to be found, allele 1 (12 bp + 85 bp + 97 bp), allele 2 (12 bp + 182 bp). In the IL-1B-511 gene, two possible alleles are expected to be found, allele 1 (190bp + 114bp), allele 2 (304 bp). In relation to the polymorphism of the IL-1RN gene, 5 possible alleles are expected to be found according to the repeated base pair sequences: allele 1 (410 bp), allele 2 (240 bp), allele 3 (500 bp), allele 4 (325 bp), allele 5 (595 bp).
次要结局
- Concentration of inflammatory response markers IL-1 beta, PGE2 and TNF-alpha(1 month after sample collection)