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Evaluation of interleukin 10, interleukin 1-beta, and tumor necrosis factor-alpha gene polymorphisms in patients with periodontitis and healthy controls



Chronic periodontitis (CP) is a prevalent infectious disease caused by an interplay between pathogens and immune responses. Gene polymorphisms are among the factors that affect susceptibility to CP. This study aimed to assess the association between CP and single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) genes.


A total of 87 patients with CP and 89 healthy controls were included in this study. Venous blood samples were obtained, and DNA was extracted and purified. Segments containing the relevant genes were amplified by polymerase chain reaction (PCR). Electrophoresis was performed after restriction fragment length polymorphism (RFLP) to determine genotype and allele frequencies.


The CP group showed significantly different allele and genotype frequencies for three out of five SNPs: IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, and IL-1ß + 3954 C/T (p < 0.05). Additionally, the frequency of the TNF-α ─ 857 AA genotype was significantly lower in patients compared with controls (p = 0.034); however, no significant differences were found in allele frequencies (p > 0.05). Logistic regression analysis revealed that carriers of IL-10 ─ 592 A allele and IL-1ß + 3954 T allele are at higher risk of CP (p < 0.001). Allele and genotype frequencies for TNF-α ─ 308 G/A did not differ significantly between patients and controls (p > 0.05).


This study showed specific genotypes of IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, IL-1ß + 3954 C/T, and TNF-α ─ 857 G/A SNPs may be associated with an increased risk of CP development.


Periodontitis is one of the most common health conditions with an estimated prevalence of 10% among the adult population worldwide [1]. It is an infectious disease of the tissues supporting teeth, characterized by progressive destruction of the tissues leading to gingival recession and/or pocket formation, and in severe cases, loss of teeth [2]. It is an inflammatory condition driven by the interactions of immune response and pathogenic microorganisms present in dental plaque [3,4,5].

There are several risk factors including smoking, diabetes mellitus, socioeconomic variables, stress, and genetic predispositions [6]. Genetic variations are among the factors that predispose individuals to periodontitis [7, 8]. Gene polymorphisms are defined as variations in the sequence of DNA and may alter the function of the gene. These variations can affect gene expression when they are located in the promoter region. As a result, polymorphisms that affect the expression of inflammatory mediators, such as cytokines, may influence the initiation and progression of inflammatory diseases [9, 10].

IL-10, known as an anti-inflammatory cytokine, plays a complex role in the pathogenesis of chronic periodontitis (CP) [11, 12]. It decreases alveolar bone loss through downregulation of osteoclastogenesis mediated by T-helper 1 [11]. At the same time, it suppresses the innate response and thus, might contribute to bacterial persistence and the following chronic infection in the region [12]. Two detected single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene, including at positions − 819 and − 592, are reported to be associated with several diseases [13,14,15,16].

Pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), affect the development of periodontitis [17, 18]. Levels of these cytokines increase in the gingival crevicular fluid and saliva of patients with periodontitis [19,20,21]. IL-1β and TNF-α contribute to bone resorption through activation of osteoclasts and stimulation of the release of other mediators associated with bone destruction [17, 18]. Two variants of the TNF-α gene, one at position − 857 and the other at − 308, are documented to increase the risk of chronic diseases namely diabetes mellitus [10].

The relationship between several SNPs and periodontitis has been questionable and more clinical data are needed to draw a reliable conclusion in this regard [22, 23]. Furthermore, it is proved that the association between gene polymorphisms and periodontitis differs based on race [24, 25]. However, there is relatively little evidence available on the Iranian population. Therefore, this study aimed to assess the association between IL-1ß, IL-10, and TNF-α gene polymorphisms and CP in an Iranian population. As genetic predisposition seems to be different for various forms of periodontitis [23], this study focused on the chronic form.

Materials and methods

The present case-control study was conducted at the Department of Periodontics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The study protocol was approved by the ethics committee (IR.SBMU.DRC.REC.1399.099). Written informed consent was obtained from all patients and demographic data were collected. The study was conducted on 87 patients with CP and 89 periodontally healthy controls. Only Iranian individuals were included and the following exclusion criteria were applied: oral diseases other than dental caries, ongoing orthodontic treatment, smoking, history of systemic diseases or medications affecting the immune system, pregnancy, lactation, diabetes mellitus, HIV infection, hepatitis, and chemotherapy.

Individuals in the control group were selected based on the criteria of having a minimum of 20 teeth with no history or current symptoms of periodontitis. The patients had at least five teeth in each quadrant, except for the third molars. CP was diagnosed based on the radiographic and clinical evaluation with the following criteria: probing pocket depth > 3 mm, clinical attachment loss ≥ 3 mm, and bleeding on probing of at least three teeth at two quadrants.

For genotype determination, a 5 cc venous blood sample was obtained from each participant and stored in EDTA-coated tubes at − 40 °C. A code was assigned to each tube and the respective patient so that the lab technicians were blinded to the group allocation. DNA was extracted using Miller’s salting-out technique, following the guidelines of the DNA extraction kit manufacturer (Bioneer, Cinnagen Company, Iran).

After the purification of DNA, segments containing the relevant gene were amplified. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) was conducted to determine genotype frequencies. Following the PCR, products were combined with specific restriction enzymes (Fermentas, Thermo Fisher Scientific, Waltham, U.S.) (Table 1), Tango buffer, and sterile distilled water, to reach the final volume of 20 μL. The solution was then incubated in half-microtiter micro tips for RFLP at 37 °C for 16 h (following the manufacturer’s guidelines). Following the incubation, the mixture was combined with 2 μL loading buffer and poured into the polyacrylamide gel’s wells. The first ladder served as a marker for the determination of DNA fragments’ length. For this purpose, 0.5 μL marker solution (50 or 100 base pair DNA ladder) was mixed with 10 μL sterilized distilled water and poured into the first well. Electrophoresis was completed within 20–30 min at a voltage of 180 v. After the electrophoresis, the polyacrylamide gel was stained with 0.1% silver nitrate or 0.5 μg/ml ethidium bromide.

Table 1 Primer sequence, restriction enzyme, and cut sequences for each gene

Data analysis was performed using SPSS Statistics 22.0 (IBM, Armonk, USA). Distribution normality was assessed with the Shapiro-Wilks test and graphical approach. Chi-square or Fisher's exact test was applied to assess the statistical significance of the differences, which was set at P value < 0.05.


This study was performed on 87 patients with periodontitis and 89 healthy controls. Table 2 demonstrates demographic data and the outcomes of clinical examination of individuals. No significant differences were found between the two groups in terms of age or sex (p = 0.471 and p = 0.651, respectively). Genotype and allele frequencies are depicted in Table 3. Patients showed significantly different allele and genotype frequencies in three out of five gene polymorphisms: IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, and IL-1ß + 3954 C/T (p < 0.05). In addition, AA genotype frequency of TNF-α ─ 857 gene was significantly lower in patients (p = 0.034). Based on logistic regression analysis, CA and AA carriers of IL-10 ─ 592 gene, and CT and TT carriers of IL-1ß + 3954 gene were more likely to present periodontitis (p < 0.001, Table 4).

Table 2 Demographic data and clinical characteristics of the subjects
Table 3 Association of IL-10, IL-1ß, and TNF-α polymorphisms with risk of periodontitis
Table 4 Logistic regression analysis of risk factors associated with periodontitis susceptibility

In the CP group, the frequency of CC, CA, and AA genotypes for IL-10 ─ 592 C/A was reported to be 32%, 53%, and 15%, respectively. These values were 60%, 39%, and 1%, respectively, in the control group. The frequency of CC genotype was significantly lower in patients compared with the controls (p < 0.001). The frequency of AA genotype was significantly higher in patients (p = 0.011). For IL-10 ─ 819 C/T, the frequency of CC, CT, and TT genotypes was 23%, 52%, and 25%, respectively, in patients, and 51%, 39%, and 10%, respectively, in controls. In patients, CC genotype was significantly less frequent (p < 0.001), while TT genotype was significantly more frequent (p = 0.008). In addition, the frequency of CC, CT, and TT genotypes for IL-1ß + 3954 C/T was 71%, 23%, and 6%, respectively, in patients, and 92%, 8%, and 0%, respectively, in controls. In patients, the frequency of CC genotype was significantly lower (< 0.001) and the frequency of CT genotype was significantly higher (p = 0.005). for TNF-α ─ 857 gene, AA genotype frequency was 39% in patients and significantly higher in controls (55%, p = 0.034). However, there was no statistically significant difference in allele frequencies between the groups. The genotype and allele frequencies of TNF-α ─ 308 G/A did not significantly differ between the groups (p > 0.05).


Several cytokines are involved in the inflammatory and immune response of connective tissue [26]. These cytokines can be associated with the onset and progression of inflammatory diseases including periodontitis [27,28,29]. Gene polymorphisms that are located in the promoter region can affect cytokine expression and thus, the risk of periodontitis. Therefore, the identification of such polymorphisms contributes to a better understanding of the molecular drives of periodontitis as well as its risk factors. Our outcomes showed that the CC genotype of IL-10 ─ 592, IL-10 ─ 819, and IL-1ß + 3954 genes and AA genotype of TNF-α ─ 857 gene have significantly lower frequency among CP patients. In contrast, IL-10 ─ 819/ TT and IL-1ß + 3954/ CT genotypes had significantly higher prevalence among these patients. This data suggest a link between the latter genotypes and periodontitis development, in a way that they might make the supportive tissue susceptible to destruction.

The role of IL-10 in periodontitis progression is a complicated issue. Its protective role of the supporting bone has been documented, which is due to the suppression of osteoclastogenesis [11, 30,31,32]. IL-10 also inhibits macrophage activation as well as pro-inflammatory cytokines such as IL-1, TNF, and IL-6 [33,34,35]. As a result, it limits the extent and period of inflammatory and immune response and can contribute to the persistence of bacteria and chronic infection in the region [12, 36, 37]. This is consistent with the studies that have shown higher levels of IL-10 in the gingival crevicular fluid of periodontitis patients [20]. Our results showed that the A allele of the IL-10 ─ 592 gene is significantly associated with CP. Considering the higher expression of IL-10 in periodontitis patients, it can be inferred that the C allele is associated with a higher expression of IL-10. In a systematic review and meta-analysis by Mashhadiabbas et al. (2021), the A allele was proved to increase risks of CP (p = 0.034), which supports our findings. To the knowledge of the authors, only one study other than the present one has evaluated IL-10 ─ 592 C/A SNP in the Iranian population, which has reported no significant association [38].

Previous studies have shown a significant relationship between IL-10 ─ 819 C/T SNP and several diseases, including Alzheimer’s disease, lung cancer, and Behcet’s disease [13,14,15,16]. We demonstrated that the T allele of the IL-10 ─ 819 gene is associated with higher risks of periodontitis. This is consistent with the outcomes of our previous study on peri-implantitis [39]. In contrast, Mashhadiabbas et al. [25] reported no significant association between risks of chronic and aggressive periodontitis with IL-10 ─ 819 C/T SNP. Differences between our outcomes and the previous studies might be attributed to racial differences [24, 25].

A significantly higher level of IL-1 β has been documented in patients with periodontitis, which decreases by clinical improvement following treatment [40]. We showed that carriers of the T allele of the IL-1ß + 3954 gene are at a higher risk for CP. Based on the latest meta-analysis on this subject by Citterio et al., the association between IL-1ß + 3954 C/T and CP has been questionable because of the methodological inconsistency of relevant studies [22]. For improvement of the methodological quality, Citterio et al. [22] suggested multicentric studies with sufficiently powered samples, stricter criteria for the groups, and adjustment for confounders.

We found no significant association between TNF-α ─ 308 G/A SNP and CP. In contrast to our findings, a recent meta-analysis by Zhang et al. [23] has reported an association between chronic and aggressive periodontitis with the A allele, particularly in the Asian subgroup. However, none of the included studies had been performed on the Iranian population with CP, which highlights the importance of inter-racial differences. To the best of our knowledge, only one similar study has been performed on Iranian patients, which indicates no significant relationship between aggressive periodontitis and TNF-α ─ 308 G/A SNP [41].

For TNF-α ─ 857 G/A SNP, our analysis revealed a significantly lower frequency of AA genotype in CP patients; however, no significant differences were observed in terms of allele frequencies. Xu et al. [42] in a meta-analysis in 2020 found no association between TNF-α ─ 857 G/A SNP and CP susceptibility.

There are several limitations to this study. Genetic studies should be conducted on a large scale, multi-center settings, with randomly selected samples, to be representative of the target population. In addition, such studies can yield better results if they are conducted prospectively. These could not be carried out in this study as it was primarily a clinic-based investigation. Therefore, more studies are required to corroborate the current results. This is particularly true for SNPs with inconsistent results across the studies, including IL-10 ─ 819 C/T, TNF-α ─ 308 G/A, and TNF-α ─ 857 SNPs. Finally, it should be noted that genetic susceptibility to CP is affected by a combinational effect of hundreds or thousands of genes, in addition to the environmental and epigenetic factors, which could be considered potential confounders [6]. Limited access to patients with CP made it challenging to evaluate the response to treatment in each genotype in terms of statistical power. It is highly recommended to assess the treatment responses in each genotype in future studies with larger sample sizes to overview and achieve the best therapeutic approaches for each genotype.


In conclusion, this study demonstrated a significant association between IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, IL-1ß + 3954 C/T, and TNF-α ─ 857 G/A SNPs and CP; however, no statistically significant relationship was found between TNF-α ─ 308 G/A SNP and CP.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.


  1. Kassebaum N, Bernabé E, Dahiya M, Bhandari B, Murray C, Marcenes W (2014) Global burden of severe periodontitis in 1990–2010: a systematic review and meta-regression. J Dent Res 93(11):1045–1053

    Article  CAS  Google Scholar 

  2. Newman MG, Carranza FA, Takei HH, Klokkevold PR (2006) Carranza’s clinical periodontology. Elsevier Brasil

    Google Scholar 

  3. Zadeh HH, Nichols FC, Miyasaki KT (1999) The role of the cell-mediated immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontitis. Periodontol 2000 20(1):239–288

    Article  CAS  Google Scholar 

  4. Kinane DF, Mooney J, Ebersole JL (1999) Humoral immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontal disease. Periodontol 2000 20(1):289–340.

    Article  CAS  Google Scholar 

  5. Shafizadeh M, Amid R, Mahmoum M, Kadkhodazadeh M (2021) Histopathological characterization of peri-implant diseases: a systematic review and meta-analysis. Arch Oral Biol 132:105288

    Article  CAS  Google Scholar 

  6. Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal diseases. Nat Rev Dis Primers 3:17038

    Article  Google Scholar 

  7. Tettamanti L, Gaudio R, Iapichino A, Mucchi D, Tagliabue A (2017) Genetic susceptibility and periodontal disease: a retrospective study on a large italian sample. ORAL Implantol 10(1):20

    Article  CAS  Google Scholar 

  8. Saremi L, Esmaeilzadeh E, Ghorashi T, Sohrabi M, EkhlasmandKermani M, Kadkhodazadeh M (2019) Association of Fc gamma-receptor genes polymorphisms with chronic periodontitis and Peri-Implantitis. J Cell Biochem 120(7):12010–12017

    Article  CAS  Google Scholar 

  9. Cullinan M, Westerman B, Hamlet S, Palmer J, Faddy M, Seymour G et al (2008) Progression of periodontal disease and interleukin-10 gene polymorphism. J Periodontal Res 43(3):328–333

    Article  CAS  Google Scholar 

  10. Ding C, Ji X, Chen X, Xu Y, Zhong L (2014) TNF-α gene promoter polymorphisms contribute to periodontitis susceptibility: evidence from 46 studies. J Clin Periodontol 41(8):748–759

    Article  CAS  Google Scholar 

  11. Zhang X, Teng Y-TA (2006) Interleukin-10 inhibits gram-negative-microbe-specific human receptor activator of NF-κB ligand-positive CD4+-Th1-cell-associated alveolar bone loss in vivo. Infect Immun 74(8):4927–4931

    Article  CAS  Google Scholar 

  12. Mege J-L, Meghari S, Honstettre A, Capo C, Raoult D (2006) The two faces of interleukin 10 in human infectious diseases. Lancet Infect Dis 6(9):557–569

    Article  CAS  Google Scholar 

  13. Shahriyari E, Vahedi L, Roshanipour N, Jafarabadi MA, Khamaneh A, Laleh MG (2019) Exploring the association of IL-10 polymorphisms in Behcet’s disease: a systematic review and meta-analysis. J Inflamm 16(1):1–10

    Article  Google Scholar 

  14. Lan X, Lan T, Faxiang Q (2015) Interleukin-10 promoter polymorphism and susceptibility to lung cancer: a systematic review and meta-analysis. Int J Clin Exp Med 8(9):15317

    CAS  Google Scholar 

  15. Lee YH, Song GG (2019) Meta-analysis of associations between interleukin-10 polymorphisms and susceptibility to Behcet’s disease. Immunol Res 67(4):424–431

    Article  CAS  Google Scholar 

  16. Di Bona D, Rizzo C, Bonaventura G, Candore G, Caruso C (2012) Association between interleukin-10 polymorphisms and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 29(4):751–759

    Article  Google Scholar 

  17. Nakamura I, Jimi E (2006) Regulation of osteoclast differentiation and function by interleukin-1. Vitam Horm 74:357–370

    Article  CAS  Google Scholar 

  18. Boyce BE, Li P, Yao Z, Zhang Q, Badell IR, Schwarz EM et al (2005) TNFα and pathologic bone resorption. Keio J Med 54(3):127–131

    Article  CAS  Google Scholar 

  19. Madureira DF, De Abreu L, Lima I, Costa GC, Lages EMB, Martins CC, Aparecida Da Silva T (2018) Tumor necrosis factor-alpha in gingival crevicular fluid as a diagnostic marker for periodontal diseases: a systematic review. J Evidence-Based Dental Pract 18(4):315–331

    Article  Google Scholar 

  20. Caldeira FID, Hidalgo MAR, De Carli Dias ML, Scarel-Caminaga RM, Pigossi SC (2021) Systematic review of ratios between disease /health periodontitis modulators and meta-analysis of their levels in gingival tissue and biological fluids. Arch Oral Biol 127:105147

    Article  CAS  Google Scholar 

  21. Gomes FI, Aragão MG, Barbosa FC, Bezerra MM, de Paulo Teixeira Pinto V, Chaves HV. (2016) Inflammatory cytokines interleukin-1β and tumour necrosis factor-α - novel biomarkers for the detection of periodontal diseases: a literature review. J Oral Maxillofac Rese 7(2):e2

    Google Scholar 

  22. Citterio F, Romano F, Ferrarotti F, Gualini G, Aimetti M (2019) Quality of methods and reporting in association studies of chronic periodontitis and IL1A -889 and IL1B +3953/4 SNPs: a systematic review. J Periodontal Res 54(5):457–467

    Article  CAS  Google Scholar 

  23. Zhang X, Zhu X, Sun W (2021) Association between tumor necrosis factor-α (G-308A) polymorphism and chronic periodontitis, aggressive periodontitis, and peri-implantitis: a meta-analysis. J Evid Based Dent Pract 21(3):101528

    Article  Google Scholar 

  24. Song GG, Choi SJ, Ji JD, Lee YH (2013) Association between tumor necrosis factor-α promoter -308 A/G, -238 A/G, interleukin-6 -174 G/C and -572 G/C polymorphisms and periodontal disease: a meta-analysis. Mol Biol Rep 40(8):5191–5203

    Article  CAS  Google Scholar 

  25. Mashhadiabbas F, Dastgheib SA, Hashemzehi A, Bahrololoomi Z, Asadian F, Neamatzadeh H et al (2021) Association of IL-10 -1082A>G, -819C>T, and -592C>a polymorphisms with susceptibility to chronic and aggressive periodontitis: a systematic review and meta-analysis. Inflammat Res Off J Eur Histam Res Soc 70(5):509–524

    CAS  Google Scholar 

  26. Greenwood D, Slack RC, Barer MR, Irving WL. Medical microbiology E-book: a guide to microbial infections: pathogenesis, immunity, laboratory diagnosis and control. With STUDENT CONSULT online access: Elsevier Health Sciences; 2012.

  27. Arora S, Ramachandra SS, Abdullah F, Gundavarapu KC (2017) Interleukin 1β (+ 3954;− 511) genotype polymorphism and its association with severe chronic generalized periodontitis in the Malaysian Population. Contemp clin Dent 8(1):102

    Article  CAS  Google Scholar 

  28. Heidari Z, Moudi B, Mahmoudzadeh-Sagheb H (2019) Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview. BMC Oral Health 19(1):1–15

    Article  Google Scholar 

  29. Shazam H, Shaikh F, Hussain Z, Majeed MM, Khan S, Khurshid Z (2020) Evaluation of osteocalcin levels in saliva of periodontitis patients and their correlation with the disease severity: a cross-sectional study. Eur J Dent 14(03):352–359

    Article  Google Scholar 

  30. Garlet GP, Martins W Jr, Fonseca BA, Ferreira BR, Silva JS (2004) Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. J Clin Periodontol 31(8):671–679

    Article  CAS  Google Scholar 

  31. Katagiri T, Takahashi N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8(3):147–159

    Article  CAS  Google Scholar 

  32. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979

    Article  CAS  Google Scholar 

  33. Cicek Ari V, Ilarslan YD, Erman B, Sarkarati B, Tezcan I, Karabulut E et al (2016) Statins and IL-1β, IL-10, and MPO levels in gingival crevicular fluid: preliminary results. Inflammation 39(4):1547–1557

    Article  CAS  Google Scholar 

  34. Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G (1993) Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med 178(6):2207–2211

    Article  CAS  Google Scholar 

  35. Moore KW et al (1993) Interleukin-10. Ann Rev Immunol 11(1):165–190

    Article  CAS  Google Scholar 

  36. Garlet G (2010) Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res 89(12):1349–1363

    Article  CAS  Google Scholar 

  37. Escalona LA, Mastromatteo P, Correnti A, Correnti M (2016) Cytokine and metalloproteinases in gingival fluid from patients with chronic periodontitis. Invest Clin 57(2):131–142

    Google Scholar 

  38. Emampanahi M, Masoudi Rad S, SaghaeianJazi M, Mansour Samaei N, Behnampour N, Mohammadi S et al (2019) Association between interleukin-10 gene polymorphisms and severe chronic periodontitis. Oral Dis 25(6):1619–1626

    Article  Google Scholar 

  39. Saremi L, Shafizadeh M, Esmaeilzadeh E, Ghaffari ME, Amid R, Kadkhodazadeh M (2021) Assessment of IL-10, IL-1ß and TNF-α gene polymorphisms in patients with peri-implantitis and healthy controls. Mol Biol Rep 48(3):2285–2290

    Article  CAS  Google Scholar 

  40. Almehmadi AH, Alghamdi F (2018) Biomarkers of alveolar bone resorption in gingival crevicular fluid:a systematic review. Arch Oral Biol 93:12–21

    Article  CAS  Google Scholar 

  41. Ebadian AR, Radvar M, Afshari JT, Sargolzaee N, Brook A, Ganjali R, et al. Gene polymorphisms of TNF-α and IL-1β are not associated with generalized aggressive periodontitis in an Iranian subpopulation. Iran J Allerg Asthma Immunol. 2013:345–51.

  42. Xu L, Liu C, Zheng Y, Huang Y, Zhong Y, Zhao Z et al (2020) Association of TNF-α-308G/A, -238G/A, -863C/A, -1031T/C, -857C/T polymorphisms with periodontitis susceptibility: evidence from a meta-analysis of 52 studies. Medicine 99(36):e21851

    Article  CAS  Google Scholar 

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by LS, MEG, RA and MK. The first draft of the manuscript was written by EA and MS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mahdi Kadkhodazadeh.

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The study protocol was approved by the ethics committee (IR.SBMU.DRC.REC.1399.099) at Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Saremi, L., Shafizadeh, M., Ghaffari, M.E. et al. Evaluation of interleukin 10, interleukin 1-beta, and tumor necrosis factor-alpha gene polymorphisms in patients with periodontitis and healthy controls. Egypt J Med Hum Genet 23, 157 (2022).

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