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Exploratory Analysis of Sex-Related Immune Gene Expression in Patients With Severe Periodontitis Cover

Exploratory Analysis of Sex-Related Immune Gene Expression in Patients With Severe Periodontitis

Open Access
|May 2026

References

  1. 1. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038. doi.org/10.1038/nrdp.2017.38
    KinaneDF StathopoulouPG PapapanouPN Periodontal diseases Nat Rev Dis Primers. 2017 3 17038 doi.org/10.1038/nrdp.2017.38
  2. 2. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44. doi.org/10.1038/nri3785
    HajishengallisG Periodontitis: from microbial immune subversion to systemic inflammation Nat Rev Immunol. 2015 15 1 30 44 doi.org/10.1038/nri3785
  3. Ebersole JL, Kirakodu SS, Nguyen LM, Gonzalez OA. Sex effects on gingival transcriptomic patterns during initiation, progression, and resolution of periodontitis. J Periodontol. 2023;94(8):1018–1031. doi:10.1002/JPER.23-0042
  4. Ebersole JL, Kirakodu SS, Nguyen LM, Gonzalez OA. Sex and Age Effects on Healthy Gingival Transcriptomic Patterns. J Dent Res. 2023;102(8):947–956. doi:10.1177/00220345231166310
  5. 5. Su X, Jin K, Zhou X, Zhang Z, Zhang C, Li Y, et al. The association between sex hormones and periodontitis among American adults: a cross-sectional study. Front Endocrinol (Lausanne). 2023;14:1125819. doi.org/10.3389/fendo.2023.1125819
    SuX JinK ZhouX ZhangZ ZhangC LiY The association between sex hormones and periodontitis among American adults: a cross-sectional study Front Endocrinol (Lausanne). 2023 14 1125819 doi.org/10.3389/fendo.2023.1125819
  6. 6. Shepherd R, Cheung AS, Pang K, Saffery R, Novakovic B. Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Front Immunol. 2021;11:604000. doi.org/10.3389/fimmu.2020.604000
    ShepherdR CheungAS PangK SafferyR NovakovicB Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics Front Immunol. 2021 11 604000 doi.org/10.3389/fimmu.2020.604000
  7. 7. Feng Z, Liao M, Zhang L. Sex differences in disease: sex chromosome and immunity. J Transl Med. 2024;22:1150. doi.org/10.1186/s12967-024-05990-2
    FengZ LiaoM ZhangL Sex differences in disease: sex chromosome and immunity J Transl Med. 2024 22 1150 doi.org/10.1186/s12967-024-05990-2
  8. 8. Cárdenas AM, Ardila LJ, Vernal R, Melgar-Rodríguez S, Hernández HG. Biomarkers of Periodontitis and Its Differential DNA Methylation and Gene Expression in Immune Cells: A Systematic Review. International Journal of Molecular Sciences. 2022; 23(19):12042. doi.org/10.3390/ijms231912042
    CárdenasAM ArdilaLJ VernalR Melgar-RodríguezS HernándezHG Biomarkers of Periodontitis and Its Differential DNA Methylation and Gene Expression in Immune Cells: A Systematic Review International Journal of Molecular Sciences 2022 23 19 12042 doi.org/10.3390/ijms231912042
  9. 9. Valerio MS, Basilakos DS, Kirkpatrick JE, Chavez M, Hathaway-Schrader J, Herbert BA, et al. Sex-based differential regulation of bacterial-induced bone resorption. J Periodontal Res. 2017;52(3):377–387. doi.org/10.1111/jre.12401
    ValerioMS BasilakosDS KirkpatrickJE ChavezM Hathaway-SchraderJ HerbertBA Sex-based differential regulation of bacterial-induced bone resorption J Periodontal Res. 2017 52 3 377 387 doi.org/10.1111/jre.12401
  10. 10. Alves VTE, Bruno MEC, Mukherjee S, Wang L, Danaher RJ, Su L, et al. Sex-related effect of aging in gingival gamma-delta T cells. J Dent Res. 2024;103(1):62–70. doi.org/10.1177/00220345231205210
    AlvesVTE BrunoMEC MukherjeeS WangL DanaherRJ SuL Sex-related effect of aging in gingival gamma-delta T cells J Dent Res. 2024 103 1 62 70 doi.org/10.1177/00220345231205210
  11. 11. Lapp CA, Thomas ME, Lewis JB. Modulation by progesterone of interleukin-6 production by gingival fibroblasts. J Periodontol. 1995;66(4):279–284. doi.org/10.1902/jop.1995.66.4.279
    LappCA ThomasME LewisJB Modulation by progesterone of interleukin-6 production by gingival fibroblasts J Periodontol. 1995 66 4 279 284 doi.org/10.1902/jop.1995.66.4.279
  12. Man Y, Qin J, Qiu H, Wang Y, Zhang X, Yan S. Hormone Replacement Therapy Relieves Periodontitis by Inhibiting Alveolar Bone Loss and Inflammation. Oral Dis. 2025;31(4):1307–1316. doi:10.1111/odi.15192
  13. Man Y, Zhang XY, Wang XZ, Liu SY, Niu FF, Yang PS. Progesterone affects periodontitis in perimenopausal women and in an experimental rat model. J Dent Sci. 2025;20(1):452–461. doi:10.1016/j.jds.2024.05.020
  14. 14. Freitag-Wolf S, Dommisch H, Graetz C, Jockel-Schneider Y, Harks I, Staufenbiel I, et al. Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men. J Clin Periodontol. 2014;41(12):1115–1121. doi.org/10.1111/jcpe.12317
    Freitag-WolfS DommischH GraetzC Jockel-SchneiderY HarksI StaufenbielI Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men J Clin Periodontol. 2014 41 12 1115 1121 doi.org/10.1111/jcpe.12317
  15. 15. Aravindraja C, Kashef MR, Vekariya KM, Ghanta RK, Karanth S, Chan EKL, Kesavalu L. Global Non-coding microRNA Profiling in Mice Infected with Partial Human Mouth Microbes (PAHMM) Using an Ecological Time-Sequential Polybacterial Periodontal Infection (ETSPPI) Model Reveals Sex-Specific Differential microRNA Expression. International Journal of Molecular Sciences. 2022; 23(9):5107. doi.org/10.3390/ijms23095107
    AravindrajaC KashefMR VekariyaKM GhantaRK KaranthS ChanEKL KesavaluL Global Non-coding microRNA Profiling in Mice Infected with Partial Human Mouth Microbes (PAHMM) Using an Ecological Time-Sequential Polybacterial Periodontal Infection (ETSPPI) Model Reveals Sex-Specific Differential microRNA Expression International Journal of Molecular Sciences 2022 23 9 5107 doi.org/10.3390/ijms23095107
  16. 16. Zhu G, Cui X, Fan L, Pan Y, Wang L. Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis. Cells. 2023; 12(1):70. doi.org/10.3390/cells12010070
    ZhuG CuiX FanL PanY WangL Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis Cells 2023 12 1 70 doi.org/10.3390/cells12010070
  17. 17. Shiau HJ, Reynolds MA. Sex differences in destructive periodontal disease: a systematic review. J Periodontol. 2010;81(10):1379–1389. doi.org/10.1902/jop.2010.100044
    ShiauHJ ReynoldsMA Sex differences in destructive periodontal disease: a systematic review J Periodontol. 2010 81 101379 1389 doi.org/10.1902/jop.2010.100044
  18. 18. Duan X, Gleason RC, Li F, Hosur KB, Duan X, Huang D, et al. Sex dimorphism in periodontitis in animal models. J Periodontal Res. 2016;51(2):196–202. doi.org/10.1111/jre.12298
    DuanX GleasonRC LiF HosurKB DuanX HuangD Sex dimorphism in periodontitis in animal models J Periodontal Res. 2016 51 2196 202 doi.org/10.1111/jre.12298
  19. 19. Tavakoli TT, Gholami F, Huang H, Gonçalves PF, Villasante-Tezanos A, Aukhil I, et al. Gender differences in immunological response of African-American juveniles with Grade C molar-incisor pattern periodontitis. J Periodontol. 2022;93(3):392–402. doi.org/10.1002/jper.21-0143
    TavakoliTT GholamiF HuangH GonçalvesPF Villasante-TezanosA AukhilI Gender differences in immunological response of African-American juveniles with Grade C molar-incisor pattern periodontitis J Periodontol. 2022 93 3392 402 doi.org/10.1002/jper.21-0143
  20. 20. Steffens JP, Wang X, Starr JR, Spolidorio LC, Van Dyke TE, Kantarci A. Associations between sex hormone levels and periodontitis in men: results from NHANES III. J Periodontol. 2015;86(10):1116–1125. doi.org/10.1902/jop.2015.140530
    SteffensJP WangX StarrJR SpolidorioLC Van DykeTE KantarciA Associations between sex hormone levels and periodontitis in men: results from NHANES III J Periodontol. 2015 86 101116 1125 doi.org/10.1902/jop.2015.140530
  21. 21. Palanisamy S. The impact of estrogen on periodontal tissue integrity and inflammation: a mini review. Front Dent Med. 2025;6:1455755. doi.org/10.3389/fdmed.2025.1455755
    PalanisamyS The impact of estrogen on periodontal tissue integrity and inflammation: a mini review Front Dent Med. 2025 6 1455755 doi.org/10.3389/fdmed.2025.1455755
  22. 22. Singh SS, Chauhan SB, Kumar A, Kumar S, Engwerda CR, Sundar S, et al. Amphiregulin in cellular physiology, health, and disease: potential use as a biomarker and therapeutic target. J Cell Physiol. 2022;237(2):1143–1156. doi.org/10.1002/jcp.30615
    SinghSS ChauhanSB KumarA KumarS EngwerdaCR SundarS Amphiregulin in cellular physiology, health, and disease: potential use as a biomarker and therapeutic target J Cell Physiol. 2022 237 21143 1156 doi.org/10.1002/jcp.30615
  23. Zaiss DMW, Gause WC, Osborne LC, Artis D. Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair. Immunity. 2015;42(2):216–226. doi:10.1016/j.immuni.2015.01.020
  24. Arpaia N, Green JA, Moltedo B, et al. A Distinct Function of Regulatory T Cells in Tissue Protection. Cell. 2015;162(5):1078–1089. doi:10.1016/j.cell.2015.08.021
  25. 25. Philpott DJ, Sorbara MT, Robertson SJ, Croitoru K, Girardin SE. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol. 2014;14(1):9–23. doi.org/10.1038/nri3565
    PhilpottDJ SorbaraMT RobertsonSJ CroitoruK GirardinSE NOD proteins: regulators of inflammation in health and disease Nat Rev Immunol. 2014 14 19 23 doi.org/10.1038/nri3565
  26. Chen G, Shaw MH, Kim YG, Nuñez G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol. 2009;4:365–398. doi:10.1146/annurev.pathol.4.110807.092239
  27. Yuan H, Zelkha S, Burkatovskaya M, Gupte R, Leeman SE, Amar S. Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss. Proc Natl Acad Sci U S A. 2013;110(52):E5059–E5068. doi:10.1073/pnas.1320862110
  28. 28. Negroni A, Pierdomenico M, Cucchiara S, Stronati L. NOD2 and inflammation: current insights. J Inflamm Res. 2018;11:49–60. doi.org/10.2147/JIR.S137606
    NegroniA PierdomenicoM CucchiaraS StronatiL NOD2 and inflammation: current insights J Inflamm Res. 2018 11 49 60 doi.org/10.2147/JIR.S137606
  29. 29. Alvarez C, Rojas C, Rojas L, Cafferata EA, Monasterio G, Vernal R. Regulatory T lymphocytes in periodontitis: a translational view. Mediators Inflamm. 2018;2018:7806912. doi.org/10.1155/2018/7806912
    AlvarezC RojasC RojasL CafferataEA MonasterioG VernalR Regulatory T lymphocytes in periodontitis: a translational view Mediators Inflamm. 2018 2018 7806912 doi.org/10.1155/2018/7806912
  30. 30. Sudo T, Okada Y, Ozaki K, Urayama K, Kanai M, Kobayashi H, et al. Association of NOD2 mutations with aggressive periodontitis. J Dent Res. 2017;96(10):1100–1105. doi.org/10.1177/0022034517715432
    SudoT OkadaY OzakiK UrayamaK KanaiM KobayashiH Association of NOD2 mutations with aggressive periodontitis J Dent Res. 2017 96 101100 1105 doi.org/10.1177/0022034517715432
  31. 31. Mizuno N, Kume K, Nagatani Y, Matsuda S, Iwata T, Ouhara K, et al. Aggressive periodontitis and NOD2 variants. J Hum Genet. 2020;65(10):841–846. doi.org/10.1038/s10038-020-0777-z
    MizunoN KumeK NagataniY MatsudaS IwataT OuharaK Aggressive periodontitis and NOD2 variants J Hum Genet. 2020 65 10841 846 doi.org/10.1038/s10038-020-0777-z
  32. 32. Chen YY, Tan L, Su XL, Chen NX, Liu Q, Feng YZ, et al. NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis. Mol Oral Microbiol. 2024;39(6):446–460. doi.org/10.1111/omi.12467
    ChenYY TanL SuXL ChenNX LiuQ FengYZ NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis Mol Oral Microbiol. 2024 39 6 446 460 doi.org/10.1111/omi.12467
  33. 33. Hu J, Dusenge MA, Ye Q, Zhao YQ, Tan L, Feng Y, et al. Role of NOD2 and hepcidin in inflammatory periapical periodontitis. BMC Oral Health. 2022;22(1):263. doi.org/10.1186/s12903-022-02286-z
    HuJ DusengeMA YeQ ZhaoYQ TanL FengY Role of NOD2 and hepcidin in inflammatory periapical periodontitis BMC Oral Health. 2022 22 1 263 doi.org/10.1186/s12903-022-02286-z
  34. 34. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Núñez G, Flavell RA. Nod2-dependent regulation of innate and adaptive immunity in the intestinal mucosa. Science. 2005;307(5710):731–734. doi.org/10.1126/science.1104911
    KobayashiKS ChamaillardM OguraY HenegariuO InoharaN NúñezG FlavellRA Nod2-dependent regulation of innate and adaptive immunity in the intestinal mucosa Science. 2005 307 5710731 734 doi.org/10.1126/science.1104911
  35. 35. Brundin PMA, Landgren BM, Fjällström P, Shamekh MM, Gustafsson JÅ, Johansson AF, et al. Expression of sex hormone receptor and immune response genes in peripheral blood mononuclear cells during the menstrual cycle. Front Endocrinol (Lausanne). 2021;12:721813. doi.org/10.3389/fendo.2021.721813
    BrundinPMA LandgrenBM FjällströmP ShamekhMM Gustafsson JohanssonAF Expression of sex hormone receptor and immune response genes in peripheral blood mononuclear cells during the menstrual cycle Front Endocrinol (Lausanne). 2021 12 721813 doi.org/10.3389/fendo.2021.721813
Language: English
Page range: 65 - 72
Published on: May 14, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 2 issues per year

© 2026 D Dimitrov, V Dosseva-Panova, I Dimova, D Nikolova, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.