Exploratory Analysis of Sex-Related Immune Gene Expression in Patients With Severe Periodontitis
By: D Dimitrov, V Dosseva-Panova, I Dimova and D Nikolova
References
- 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.
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
- 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
- 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.
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.
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.
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.
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.
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.
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.
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
- 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
- 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.
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.
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.
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.
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.
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.
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.
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.
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.
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
- 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
- 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.
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
- 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
- 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.
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.
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.
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.
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.
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.
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.
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.
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 GustafssonJÅ 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
DOI: https://doi.org/10.2478/bjmg-2025-00017 | Journal eISSN: 2199-5761
Language: English
Page range: 65 - 72
Published on: May 14, 2026
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 issues per year
Keywords:
Related subjects:
© 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.