Analysis of Genetic Variations in Patients With Peri-implantitis

NCT04807725 | Unknown

• 1 other identifier: PHDJMC
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Peri-Implantitis

Keywords

peri-implantitis; gene polymorphisms; interleukin-1; dental implants

Outcome Measures

Primary Outcomes (1)

• Frequency of Participants with polymorphism in the IL-1 gene cluster

  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).

  1 month after sample collection

Secondary Outcomes (1)

• Concentration of inflammatory response markers IL-1 beta, PGE2 and TNF-alpha

  1 month after sample collection

Study Arms (2)

Peri-implant health

Includes patients with peri implant mucosa without inflammatory signs and absence of peri-implant bone loss.

Genetic: Analysis of genetic polymorphisms; Other: Biochemical analysis

Peri-implantitis

Includes patients with bleeding and / or suppuration on probing, probing depth equal or greater than 6mm and bone loss equal to or greater than 3mm.

Genetic: Analysis of genetic polymorphisms; Other: Biochemical analysis

Interventions

Analysis of genetic polymorphisms GENETIC

For the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab. The genetic analysis will be done with the DNA extraction technique followed by PCR-RFLP techniques (polymerase chain reaction followed by restriction fragment length polymorphism).

Peri-implant health; Peri-implantitis

Biochemical analysis OTHER

For the biochemical analysis of the inflammatory mediators IL-1beta, 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.

Peri-implant health; Peri-implantitis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Egas Moniz - Cooperativa de Ensino Superior, CRL: lead
• Oral Reconstruction Foudation: collaborator

Study Sites (1)

Instituto Universitário Egas Moniz

Almada, Monte de Caparica, 2829-511, Portugal

RECRUITING

Related Publications (17)

• Chen X, Zhao Y. Genetic Involvement in Dental Implant Failure: Association With Polymorphisms of Genes Modulating Inflammatory Responses and Bone Metabolism. J Oral Implantol. 2019 Aug;45(4):318-326. doi: 10.1563/aaid-joi-D-18-00212. Epub 2019 Jun 17.

  PMID: 31207194 BACKGROUND

• Duarte PM, de Mendonca AC, Maximo MB, Santos VR, Bastos MF, Nociti Junior FH. Differential cytokine expressions affect the severity of peri-implant disease. Clin Oral Implants Res. 2009 May;20(5):514-20. doi: 10.1111/j.1600-0501.2008.01680.x. Epub 2009 Mar 11.

  PMID: 19302394 BACKGROUND

• Feloutzis A, Lang NP, Tonetti MS, Burgin W, Bragger U, Buser D, Duff GW, Kornman KS. IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population. Clin Oral Implants Res. 2003 Feb;14(1):10-7. doi: 10.1034/j.1600-0501.2003.140102.x.

  PMID: 12562360 BACKGROUND

• Gruica B, Wang HY, Lang NP, Buser D. Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated implants. Clin Oral Implants Res. 2004 Aug;15(4):393-400. doi: 10.1111/j.1600-0501.2004.01026.x.

  PMID: 15248873 BACKGROUND

• Lachmann S, Kimmerle-Muller E, Axmann D, Scheideler L, Weber H, Haas R. Associations between peri-implant crevicular fluid volume, concentrations of crevicular inflammatory mediators, and composite IL-1A -889 and IL-1B +3954 genotype. A cross-sectional study on implant recall patients with and without clinical signs of peri-implantitis. Clin Oral Implants Res. 2007 Apr;18(2):212-23. doi: 10.1111/j.1600-0501.2006.01322.x.

  PMID: 17348886 BACKGROUND

• Petkovic-Curcin A, Zeljic K, Cikota-Aleksic B, Dakovic D, Tatic Z, Magic Z. Association of Cytokine Gene Polymorphism with Peri-implantitis Risk. Int J Oral Maxillofac Implants. 2017 Sep/Oct;32(5):e241-e248. doi: 10.11607/jomi.5814.

  PMID: 28906511 BACKGROUND

• He K, Jian F, He T, Tang H, Huang B, Wei N. Analysis of the association of TNF-alpha, IL-1A, and IL-1B polymorphisms with peri-implantitis in a Chinese non-smoking population. Clin Oral Investig. 2020 Feb;24(2):693-699. doi: 10.1007/s00784-019-02968-z. Epub 2019 May 24.

  PMID: 31127430 BACKGROUND

• McDowell TL, Symons JA, Ploski R, Forre O, Duff GW. A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism. Arthritis Rheum. 1995 Feb;38(2):221-8. doi: 10.1002/art.1780380210.

  PMID: 7848312 BACKGROUND

• Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet. 1993 May;91(4):403-4. doi: 10.1007/BF00217368.

  PMID: 8500797 BACKGROUND

• Hamdy AA, Ebrahem MA. The effect of interleukin-1 allele 2 genotype (IL-1a(-889) and IL-1b(+3954)) on the individual's susceptibility to peri-implantitis: case-control study. J Oral Implantol. 2011 Jun;37(3):325-34. doi: 10.1563/AAID-JOI-D-09-00117.1. Epub 2010 Jun 16.

  PMID: 20594066 BACKGROUND

• Dereka X, Mardas N, Chin S, Petrie A, Donos N. A systematic review on the association between genetic predisposition and dental implant biological complications. Clin Oral Implants Res. 2012 Jul;23(7):775-88. doi: 10.1111/j.1600-0501.2011.02329.x. Epub 2011 Dec 12.

  PMID: 22151432 BACKGROUND

• Laine ML, Leonhardt A, Roos-Jansaker AM, Pena AS, van Winkelhoff AJ, Winkel EG, Renvert S. IL-1RN gene polymorphism is associated with peri-implantitis. Clin Oral Implants Res. 2006 Aug;17(4):380-5. doi: 10.1111/j.1600-0501.2006.01249.x.

  PMID: 16907768 BACKGROUND

• Huynh-Ba G, Lang NP, Tonetti MS, Zwahlen M, Salvi GE. Association of the composite IL-1 genotype with peri-implantitis: a systematic review. Clin Oral Implants Res. 2008 Nov;19(11):1154-62. doi: 10.1111/j.1600-0501.2008.01596.x.

  PMID: 18983319 BACKGROUND

• Andreiotelli M, Koutayas SO, Madianos PN, Strub JR. Relationship between interleukin-1 genotype and peri-implantitis: a literature review. Quintessence Int. 2008 Apr;39(4):289-98.

  PMID: 19081897 BACKGROUND

• Liao J, Li C, Wang Y, Ten M, Sun X, Tian A, Zhang Q, Liang X. Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure. Mol Biol Rep. 2014 May;41(5):2789-98. doi: 10.1007/s11033-014-3133-6. Epub 2014 Jan 23.

  PMID: 24452718 BACKGROUND

• Fourmousis I, Vlachos M. Genetic Risk Factors for the Development of Periimplantitis. Implant Dent. 2019 Apr;28(2):103-114. doi: 10.1097/ID.0000000000000874.

  PMID: 30865053 BACKGROUND

• Vaz P, Gallas MM, Braga AC, Sampaio-Fernandes JC, Felino A, Tavares P. IL1 gene polymorphisms and unsuccessful dental implants. Clin Oral Implants Res. 2012 Dec;23(12):1404-13. doi: 10.1111/j.1600-0501.2011.02322.x. Epub 2011 Nov 10.

  PMID: 22092925 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

The specimens to be retained will be cells from the oral mucosa.

MeSH Terms

Conditions

Peri-Implantitis

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Ricardo Alves, Phd

  Egas Moniz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ricardo Alves, Phd

CONTACT

00351212946767; ralves@egasmoniz.edu.pt

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 19, 2021
• Study Start: March 9, 2021
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: March 23, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)