A pilot case-control study of the association of vitamin D-related gene variants with peri-implantitis
DOI:
https://doi.org/10.2298/ABS241227007MKeywords:
vitamin D, vitamin D receptor, CYP27B1, peri-implantitis, genetic polymorphism, RXRAAbstract
Paper description:
- This pilot case-control study explored whether genetic variants in vitamin D-related genes, vitamin D receptor (VDR), retinoid X receptor alpha (RXRA), and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), can serve as risk markers for peri-implantitis development.
- The study enrolled 82 patients with dental implants, 30 had peri-implantitis, and 52 exhibited healthy peri-implant tissues.
- Genetic variants (VDR rs2228570, RXRA rs3118523, rs7864987, and CYP27B1 rs4646536) were analyzed using Real-Time PCR to determine their association with peri-implantitis.
- No significant differences in genotype distributions between peri-implantitis and healthy groups were observed, suggesting that genetic variants are unreliable markers for peri-implantitis susceptibility.
Abstract: This pilot case-control study investigated whether variants in vitamin D-related genes can be used to predict the occurrence of peri-implantitis. Eighty-two patients with at least one dental implant were enrolled. Thirty patients (36.6%) were diagnosed with peri-implantitis, whereas 52 (63.4%) had healthy peri-implant tissues. Clinical parameters, risk factors (history of periodontitis, smoking), and genetic factors were assessed. A buccal mucosa swab was taken for DNA analysis. Four variants in three vitamin D-related genes, VDR (rs2228570), retinoid X receptor alpha (RXRA) (rs3118523, rs7864987), and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) (rs4646536) were genotyped by real-time PCR. There was no difference in the genotype distribution of the variants VDR rs2228570 (P=0.410), RXRA rs3118523, rs7864987 (P=0.789 and P=0.144, respectively), and CYP27B1 rs4646536 (P=0.562) between patients with healthy peri-implant tissues and those affected by peri-implantitis. History of periodontitis, a modified plaque index (mPI), modified bleeding index (mBI), peri-implant pocket depth, and implant location were associated with peri-implantitis incidence. In patients with peri-implantitis, CYP27B1 rs4646536 was associated with mBI (P=0.040), and RXRA rs7864987 was associated with implant position (P=0.009). We conclude that the variants of vitamin D-related genes, VDR, RXRA, and CYP27B1, cannot be used as molecular markers for peri-implantitis.
Downloads
References
Buser D, Sennerby L, De Bruyn H. Modern implant dentistry based on osseointegration: 50 years of progress, current trends and open questions. Periodontol 2000. 2017;73(1):7-21. https://doi.org/10.1111/prd.12185
Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol. 2018;89 Suppl 1:S267-s90. https://doi.org/10.1002/jper.16-0350
Renvert S, Quirynen M. Risk indicators for peri-implantitis. A narrative review. Clin Oral Implants Res. 2015;26 Suppl 11:15-44. https://doi.org/10.1111/clr.12636
Fourmousis I, Vlachos M. Genetic Risk Factors for the Development of Periimplantitis. Implant Dent. 2019;28(2):103-14. https://doi.org/10.1097/id.0000000000000874
Eguia Del Valle A, López-Vicente J, Martínez-Conde R, Aguirre-Zorzano LA. Current understanding of genetic polymorphisms as biomarkers for risk of biological complications in implantology. J Clin Exp Dent. 2018;10(10):e1029-e39. https://doi.org/10.4317/jced.55141
Lin R. Crosstalk between Vitamin D Metabolism, VDR Signalling, and Innate Immunity. BioMed research international. 2016;2016:1375858-. https://doi.org/10.1155/2016/1375858
Martelli FS, Martelli M, Rosati C, Fanti E. Vitamin D: relevance in dental practice. Clin Cases Miner Bone Metab. 2014;11(1):15-9.
Chen J, Tang Z, Slominski AT, Li W, Żmijewski MA, Liu Y, Chen J. Vitamin D and its analogs as anticancer and anti-inflammatory agents. Eur J Med Chem. 2020;207:112738. https://doi.org/10.1016/j.ejmech.2020.112738
Bryce G, MacBeth N. Vitamin D deficiency as a suspected causative factor in the failure of an immediately placed dental implant: a case report. J R Nav Med Serv. 2014;100(3):328-32.
Insua A, Monje A, Wang HL, Miron RJ. Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss. J Biomed Mater Res A. 2017;105(7):2075-89. https://doi.org/10.1002/jbm.a.36060
Kelly J, Lin A, Wang CJ, Park S, Nishimura I. Vitamin D and bone physiology: demonstration of vitamin D deficiency in an implant osseointegration rat model. J Prosthodont. 2009;18(6):473-8. https://doi.org/10.1111/j.1532-849X.2009.00446.x
Pourshahidi S, Yousefain M. The Relationship Between Serum Level of Vitamin D3 and Osseointegration Around the Dental Implant. J Oral Implantol. 2021;47(1):88-90. https://doi.org/10.1563/aaid-joi-D-19-00341
Guido Mangano F, Ghertasi Oskouei S. Low serum vitamin D and early dental implant failure: Is there a connection? A retrospective clinical study on 1740 implants placed in 885 patients. 2018;12(3):174-82. https://doi.org/10.15171/joddd.2018.027
Acipinar S, Karsiyaka Hendek M. Evaluation of FGF-23 and 25(OH)D(3) levels in peri-implant sulcus fluid in peri-implant health and diseases. Clin Implant Dent Relat Res. 2019;21(5):1106-12. https://doi.org/10.1111/cid.12832
Ustaoğlu G, Erdal E. Relationship between risk markers for cardiovascular disease and peri-implant diseases. Int J Implant Dent. 2020;6(1):73. https://doi.org/10.1186/s40729-020-00273-z
Sanz M, Chapple IL. Clinical research on peri-implant diseases: consensus report of Working Group 4. J Clin Periodontol. 2012;39 Suppl 12:202-6. https://doi.org/10.1111/j.1600-051X.2011.01837.x
Mombelli A, Lang NP. Clinical parameters for the evaluation of dental implants. Periodontol 2000. 1994;4:81-6. https://doi.org/10.1111/j.1600-0757.1994.tb00008.x
Kan JY, Rungcharassaeng K, Umezu K, Kois JC. Dimensions of peri-implant mucosa: an evaluation of maxillary anterior single implants in humans. J Periodontol. 2003;74(4):557-62. https://doi.org/10.1902/jop.2003.74.4.557
Rakasevic D, Lazic Z, Soldatovic I, Scepanovic M, Gabric D. Influence of titanium implant macrodesign on peri-implantitis occurrence: a cross-sectional study. Clin Oral Investig. 2022;26(8):5237-46. https://doi.org/10.1007/s00784-022-04492-z
Xu HM, Xu LF, Hou TT, Luo LF, Chen GB, Sun XW, Lou XY. GMDR: Versatile Software for Detecting Gene-Gene and Gene-Environ- ment Interactions Underlying Complex Traits. Curr Genomics. 2016;17(5):396-402. https://doi.org/10.2174/1389202917666160513102612
Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41(4):1149-60. https://doi.org/10.3758/brm.41.4.1149
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175-91. https://doi.org/10.3758/bf03193146
Cohen J. Statistical Power Analysis for the Behavioral Sciences 2nd. ed: Lawrence Erlbaum Associates; 1988.
He K, Jian F, He T, Tang H, Huang B, Wei N. Analysis of the association of TNF-α, IL-1A, and IL-1B polymorphisms with peri-implantitis in a Chinese non-smoking population. Clin Oral Investig. 2020;24(2):693-9. https://doi.org/10.1007/s00784-019-02968-z
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;32(5):e241-e8. https://doi.org/10.11607/jomi.5814
Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol. 2001;177(1-2):145-59. https://doi.org/10.1016/s0303-7207(01)00406-3
Marian D, Rusu D, Stratul SI, Calniceanu H, Sculean A, Anghel A. Association of Vitamin D Receptor Gene Polymorphisms with Chronic Periodontitis in a Population in Western Romania. Oral Health Prev Dent. 2019;17(2):157-65. https://doi.org/10.3290/j.ohpd.a39738
Naito M, Miyaki K, Naito T, Zhang L, Hoshi K, Hara A, Masaki K, Tohyama S, Muramatsu M, Hamajima N, Nakayama T. Association between vitamin D receptor gene haplotypes and chronic periodontitis among Japanese men. Int J Med Sci. 2007;4(4):216-22. https://doi.org/10.7150/ijms.4.216
Park KS, Nam JH, Choi J. The short vitamin D receptor is associated with increased risk for generalized aggressive periodontitis. J Clin Periodontol. 2006;33(8):524-8. https://doi.org/10.1111/j.1600-051X.2006.00944.x
Alvim-Pereira F, Montes CC, Thomé G, Olandoski M, Trevilatto PC. Analysis of association of clinical aspects and vitamin D receptor gene polymorphism with dental implant loss. Clin Oral Implants Res. 2008;19(8):786-95. https://doi.org/10.1111/j.1600-0501.2008.01532.x
Munhoz Pereira T, Alvim-Pereira F. A complete physical mapping of the vitamin D receptor gene for dental implant loss: A pilot study. Clin Oral Implants Res. 2019;30(12):1165-78. https://doi.org/10.1111/clr.13529
Chantarangsu S, Sura T, Mongkornkarn S, Donsakul K, Torrungruang K. Vitamin D Receptor Gene Polymorphism and Smoking in the Risk of Chronic Periodontitis. J Periodontol. 2016;87(11):1343-51. https://doi.org/10.1902/jop.2016.160222
Torrungruang K, Chantarangsu S, Sura T, Thienpramuk L. Interplay between vitamin D receptor FokI polymorphism and smoking influences Porphyromonas gingivalis proportions in subgingival plaque. J Clin Periodontol. 2020;47(8):912-20. https://doi.org/10.1111/jcpe.13307
Wang C, Zhao H, Xiao L, Xie C, Fan W, Sun S, Xie B, Zhang J. Association between vitamin D receptor gene polymorphisms and severe chronic periodontitis in a Chinese population. J Periodontol. 2009;80(4):603-8. https://doi.org/10.1902/jop.2009.080465
Taskan MM, Gevrek F. PPAR-γ, RXR, VDR, and COX-2 Expressions in gingival tissue samples of healthy individuals, periodontitis and peri-implantitis patients. Niger J Clin Pract. 2020;23(1):46-53. https://doi.org/10.4103/njcp.njcp_349_19
Yu S, Li X, Wang Y, Mao Z, Xie Y, Zhang L, Wang C, Li W. Family-based Association between Allele T of rs4646536 in CYP27B1 and vitamin D deficiency. J Clin Lab Anal. 2019;33(6):e22898. https://doi.org/10.1002/jcla.22898
Jansson L, Lavstedt S. Influence of smoking on marginal bone loss and tooth loss--a prospective study over 20 years. J Clin Periodontol. 2002;29(8):750-6. https://doi.org/10.1034/j.1600-051x.2002.290812.x
Chrcanovic BR, Albrektsson T, Wennerberg A. Smoking and dental implants: A systematic review and meta-analysis. J Dent. 2015;43(5):487-98. https://doi.org/10.1016/j.jdent.2015.03.003
Ferrantino L, Tironi F, Pieroni S, Sironi A, Simion M. A Clinical and Radiographic Retrospective Study on 223 Anodized Surface Implants with a 5- to 17-Year Follow-up. Int J Periodontics Restorative Dent. 2019;39(6):799-807. https://doi.org/10.11607/prd.4330
Rakašević D, Lazić Z, Rakonjac B, Soldatović I, Janković S, Magić M, Aleksić Z. Efficiency of photodynamic therapy in the treatment of peri-implantitis – A three-month randomized controlled clinical trial. Srp Arh Celok Lek. 2016;144(9-10):478-84.
Pimentel SP, Shiota R, Cirano FR, Casarin RCV, Pecorari VGA, Casati MZ, Haas AN, Ribeiro FV. Occurrence of peri-implant diseases and risk indicators at the patient and implant levels: A multilevel cross-sectional study. J Periodontol. 2018;89(9):1091-100. https://doi.org/10.1002/jper.17-0599
Vignoletti F, Di Domenico GL, Di Martino M, Montero E. Prevalence and risk indicators of peri-implantitis in a sample of university-based dental patients in Italy: A cross-sectional study. J Clin Periodontol. 2019;46(5):597-605. https://doi.org/10.1111/jcpe.13111
Kordbacheh Changi K, Finkelstein J, Papapanou PN. Peri-implantitis prevalence, incidence rate, and risk factors: A study of electronic health records at a U.S. dental school. Clin Oral Implants Res. 2019;30(4):306-14. https://doi.org/10.1111/clr.13416
Rodrigo D, Martin C, Sanz M. Biological complications and peri-implant clinical and radiographic changes at immediately placed dental implants. A prospective 5-year cohort study. Clin Oral Implants Res. 2012;23(10):1224-31. https://doi.org/10.1111/j.1600-0501.2011.02294.x
Messias A, Nicolau P, Guerra F. Titanium dental implants with different collar design and surface modifications: A systematic review on survival rates and marginal bone levels. Clin Oral Implants Res. 2019;30(1):20-48. https://doi.org/10.1111/clr.13389
Belibasakis GN, Manoil D. Microbial Community-Driven Etiopathogenesis of Peri-Implantitis. Journal of dental research. 2021;100(1):21-8. https://doi.org/10.1177/0022034520949851
Ghensi P, Manghi P, Zolfo M. Strong oral plaque microbiome signatures for dental implant diseases identified by strain-resolution metagenomics. NPJ Biofilms Microbiomes. 2020;6(1):47. https://doi.org/10.1038/s41522-020-00155-7
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Marko Magić, Zoran Lazić, Stevo Jovandić, Dragana Rakašević, Katarina Zeljic
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.
