Impact of miR-146a-3p rs2910164 polymorphism on peri-implantitis susceptibility and target gene-mediated inflammatory responses
DOI:
https://doi.org/10.2340/aos.v85.45995Keywords:
Peri-implantitis, miRNA, SNP, polymorphism, susceptibilityAbstract
Objectives: This study investigated the association between miR-146a-3p rs2910164 polymorphism and peri-implantitis (PI) susceptibility in the Han Chinese population, as well as the potential mechanisms underlying PI progression.
Material and Methods: 183 PI patients and 219 individuals with healthy implants were enrolled. Quantitative polymerase chain reaction was used to detect miR-146a-3p expression levels and analyze the impact of rs2910164 genotypes on these levels. The study compared the association between rs2910164 polymorphism and PI susceptibility, evaluated participants’ periodontal health status, and predicted miR-146a-3p target genes via bioinformatics methods, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) enrichment analyses. The regulatory relationship between miR-146a-3p and ITBG7 was validated by dual luciferase assays.
Results: miR-146a-3p expression was elevated in PI patients, with significantly higher levels in those carrying the CG/GG genotypes of rs2910164. Additionally, the GG genotype and G allele of rs2910164 were more prevalent in PI patients, who also exhibited poorer periodontal status. The GG genotype and G allele were identified as risk factors for PI. miR-146a-3p may contribute to PI progression by regulating inflammation-related signaling pathways. The existence of miR-146a-3p and ITBG7 had a negative regulatory relationship.
Conclusion: The miR-146a-3p rs2910164 polymorphism holds promise as a potential biomarker for predicting PI occurrence. miR-146a-3p might modulate inflammation-related signaling pathways via ITBG7 and may play a role in the regulation of PI progression.
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References
Wei X, Qian S, Yang Y, Mo J. Microbiome-based therapies for periodontitis and peri-implantitis. Oral Dis. 2024;30(5):2838–57. DOI: https://doi.org/10.1111/odi.14782
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;45(4):318–26. DOI: https://doi.org/10.1563/aaid-joi-D-18-00212
Dopytalska K, Czaplicka A, Szymańska E, Walecka I. The essential role of microRNAs in inflammatory and autoimmune skin diseases – a review. Int J Mol Sci. 2023;24(11):9130. DOI: https://doi.org/10.3390/ijms24119130
Palideh A, Vaghari-Tabari M, Nosrati Andevari A, Qujeq D, Asemi Z, Alemi F, et al. MicroRNAs and periodontal disease: helpful therapeutic targets? Adv Pharm Bull. 2023;13(3):423–34. DOI: https://doi.org/10.34172/apb.2023.048
Almiñana-Pastor PJ, Alpiste-Illueca FM, Micó-Martinez P, García-Giménez JL, García-López E, López-Roldán A. MicroRNAs in gingival crevicular fluid: an observational case-control study of differential expression in periodontitis. Non-coding RNA. 2023;9(6):73. DOI: https://doi.org/10.3390/ncrna9060073
Taheri M, Khoshbakht T, Hussen BM, Abdullah ST, Ghafouri-Fard S, Sayad A. Emerging role of miRNAs in the pathogenesis of periodontitis. Curr Stem Cell Res Ther. 2024;19(4):427–48. DOI: https://doi.org/10.2174/1574888X17666220617103820
Darby I. Risk factors for periodontitis & peri-implantitis. Periodontology 2000. 2022;90(1):9–12. DOI: https://doi.org/10.1111/prd.12447
Hamed MN, Abdulbaqi HR. Expression of miRNAs (146a and 155) in human peri-implant tissue affected by peri-implantitis: a case control study. BMC Oral Health. 2024;24(1):856. DOI: https://doi.org/10.1186/s12903-024-04579-x
Ryan BM. microRNAs in cancer susceptibility. Adv Cancer Res. 2017;135:151–71. DOI: https://doi.org/10.1016/bs.acr.2017.06.004
Kotlarek M, Kubiak A, Czetwertyńska M, Świerniak M, Gierlikowski W, Kolanowska M, et al. The rs2910164 genetic variant of miR-146a-3p is associated with increased overall mortality in patients with follicular variant papillary thyroid carcinoma. Int J Mol Sci. 2018;19(3):655. DOI: https://doi.org/10.3390/ijms19030655
McVeigh TP, Mulligan RJ, McVeigh UM, Owens PW, Miller N, Bell M, et al. Investigating the association of rs2910164 with cancer predisposition in an Irish cohort. Endocr Connect. 2017;6(8):614–24. DOI: https://doi.org/10.1530/EC-17-0196
Gao X, Zhu Z, Zhang S. miR-146a rs2910164 polymorphism and the risk of colorectal cancer in Chinese population. J Cancer Res Ther. 2018;14(Supplement):S97–9. DOI: https://doi.org/10.4103/0973-1482.165864
Yin Z, Cui Z, Ren Y, Xia L, Li H, Zhou B. MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females. Oncotarget. 2017;8(2):2275–83. DOI: https://doi.org/10.18632/oncotarget.13722
Zhang E, Xu Z, Duan W, Huang S, Lu L. Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population. PLoS One. 2017;12(6):e0176044. DOI: https://doi.org/10.1371/journal.pone.0176044
Keewan E, Naser SA. MiR-146a rs2910164 G > C polymorphism modulates Notch-1/IL-6 signaling during infection: a possible risk factor for Crohn’s disease. Gut Pathogens. 2020;12:48. DOI: https://doi.org/10.1186/s13099-020-00387-0
Ghorab RA, Fouad SH, Sherief AF, El-Sehsah EM, Shamloul S, Taha SI. MiR-146a (rs2910164) gene polymorphism and its impact on circulating MiR-146a levels in patients with inflammatory bowel diseases. Inflammation. 2024;48(3):1193-1205. DOI: https://doi.org/10.1007/s10753-024-02108-0
Turkmen M, Firatli E. The study of genetic predisposition on periodontitis and peri-implantitis. Niger J Clin Pract. 2022;25(11):1799–804. DOI: https://doi.org/10.4103/njcp.njcp_19_22
Singh RP, Massachi I, Manickavel S, Singh S, Rao NP, Hasan S, et al. The role of miRNA in inflammation and autoimmunity. Autoimmun Rev. 2013;12(12):1160–5. DOI: https://doi.org/10.1016/j.autrev.2013.07.003
Xiao Y, Qiao W, Wang X, Sun L, Ren W. MiR-146a mediates TLR-4 signaling pathway to affect myocardial fibrosis in rat constrictive pericarditis model. J Thorac Dis. 2021;13(2):935–45. DOI: https://doi.org/10.21037/jtd-20-2716
Xia C, Zhu K, Zhang Y, Chen J, Yu C, Gao T, et al. Serum exosome-derived miR-146a-3p promotes macrophage M2 polarization in allergic rhinitis by targeting VAV3 via PI3K/AKT/mTOR pathway. Int Immunopharmacol. 2023;124(Pt B):110997. DOI: https://doi.org/10.1016/j.intimp.2023.110997
Subbarao KC, Nattuthurai GS, Sundararajan SK, Sujith I, Joseph J, Syedshah YP. Gingival crevicular fluid: an overview. J Pharm Bioall Sci. 2019;11(Suppl 2):S135–9. DOI: https://doi.org/10.4103/JPBS.JPBS_56_19
Zhao Z, Attanasio C, Pedano MS, Cadenas de Llano-Pérula M. Comparison of human dental tissue RNA extraction methods for RNA sequencing. Archiv Oral Biol. 2023;148:105646. DOI: https://doi.org/10.1016/j.archoralbio.2023.105646
Wang Y, Ru J, Meng X, Song J, Jiang Q, Li S, et al. Role of SNPs in the biogenesis of mature miRNAs. BioMed Res Int. 2021;2021:2403418. DOI: https://doi.org/10.1155/2021/2403418
Cardoso JM, Ribeiro AC, Palos C, Proença L, Noronha S, Alves RC. Association between IL-1A and IL-1B gene polymorphisms with peri-implantitis in a Portuguese population-a pilot study. PeerJ. 2022;10:e13729. DOI: https://doi.org/10.7717/peerj.13729
Jamshidy L, Tadakamadla SK, Choubsaz P, Sadeghi M, Tadakamadla J. Association of IL-10 and TNF-α polymorphisms with dental peri-implant disease risk: a meta-analysis, meta-regression, and trial sequential analysis. Int J Environ Res Public Health. 2021;18(14):7697. DOI: https://doi.org/10.3390/ijerph18147697
Kadkhodazadeh M, Jafari AR, Amid R, Ebadian AR, Alipour MM, Mollaverdi F, et al. MiR146a and MiR499 gene polymorphisms in Iranian periodontitis and peri-implantitis patients. J Long Term Eff Med Implants. 2013;23(1):9–16. DOI: https://doi.org/10.1615/JLongTermEffMedImplants.2013007073
Kookli K, Soleimani KT, Amr EF, Ehymayed HM, Zabibah RS, Daminova SB, et al. Role of microRNA-146a in cancer development by regulating apoptosis. Pathol Res Pract. 2024;254:155050. DOI: https://doi.org/10.1016/j.prp.2023.155050
Sawyer N, Watkins AM, Arora PS. Protein domain mimics as modulators of protein-protein interactions. Acc Chem Res. 2017;50(6):1313–22. DOI: https://doi.org/10.1021/acs.accounts.7b00130
Zaripova LN, Midgley A, Christmas SE, Beresford MW, Pain C, Baildam EM, et al. Mesenchymal stem cells in the pathogenesis and therapy of autoimmune and autoinflammatory diseases. Int J Mol Sci. 2023;24(22):16040. DOI: https://doi.org/10.3390/ijms242216040
Zusso M, Lunardi V, Franceschini D, Pagetta A, Lo R, Stifani S, et al. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J Neuroinflamm. 2019;16(1):148. DOI: https://doi.org/10.1186/s12974-019-1538-9
Króliczewski J, Sobolewska A, Lejnowski D, Collawn JF, Bartoszewski R. microRNA single polynucleotide polymorphism influences on microRNA biogenesis and mRNA target specificity. Gene. 2018;640:66–72. DOI: https://doi.org/10.1016/j.gene.2017.10.021
de Araújo MF, Etchebehere RM, de Melo MLR, Beghini M, Severino VO, de Castro Côbo E, et al. Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis. Pathol Res Pract. 2017;213(9):1097–101. DOI: https://doi.org/10.1016/j.prp.2017.07.020
Feng X, Peng D, Qiu Y, Guo Q, Zhang X, Li Z, et al. Identification and validation of aging- and endoplasmic reticulum stress-related genes in periodontitis using a competing endogenous RNA network. Inflammation. 2024;48(3):1326-1349. DOI: https://doi.org/10.1007/s10753-024-02124-0
Baran A, Nowowiejska J, Kamiński TW, Krahel JA, Flisiak I. Circulating MAdCAM-1 and ITGB7 in patients with plaque psoriasis and eruptive lichen planus-preliminary data. Biology. 2021;10(11):1129. DOI: https://doi.org/10.3390/biology10111129
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