IL-8 and its polymorphisms are involved in multiple acute and chronic inflammatory processes including pathological changes to surrounding structures of the teeth called periodontal diseases or periodontitis. The aim of this manuscript was to systematically review studies from 2006 to 2021 on IL-8 polymorphisms and their association with periodontitis. Literature analysis was done following the PRISMA protocol guidance using articles not older than 15 years (2006-2021). The search was carried out using PubMed (MEDLINE), ScienceDirect and Wiley Online Library databases. For the focus question, the PICO (population (P), intervention (I), control (C), and outcome (O)) study design protocol was used, and the following question was formulated: are IL-8 gene polymorphisms associated with periodontitis? A total of 2422 articles were found at the beginning of the search. After applying the inclusion and exclusion criteria, screening, and full-text article exclusion with reasons, 31 studies were included in the analysis. In conclusion, IL-8 and its gene polymorphisms are associated with an increased risk of periodontal diseases.

Department of Prosthodontics Lithuanian University of Health Sciences Kaunas Lithuania

Institute of Neuroscience Lithuanian University of Health Sciences Kaunas Lithuania

Zobrazit více v PubMed

Kaur G, Grover V, Bhaskar N, Kaur RK, Jain A. Periodontal Infectogenomics. Inflamm Regen 2018;38:8. PubMed DOI

Gasner NS, Schure RS. Periodontal Disease. [Updated 2020 May 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554590/

Data and statistics [Internet]. Euro.who.int. 2021. Accessed: 18 May 2021: https://www.euro.who.int/en/health-topics/disease-prevention/oral-health/data-and-statistics

Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol 2000;83(1):26-39. PubMed DOI

Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, Taylor GW, Page RC, Beck JD, Genco RJ. Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. J Periodontol 2015;86(5):611-22. PubMed DOI

Gerritsen AE, Allen PF, Witter DJ, Bronkhorst EM, Creugers NH. Tooth loss and oral health-related quality of life: a systematic review and meta-analysis. Health Qual Life Outcomes 2010;5;8:126. PubMed DOI

Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol 2018;89:S159-S172. PubMed DOI

Mehrotra N, Singh S. Periodontitis. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541126/

Michaud DS, Fu Z, Shi J, Chung M. Periodontal Disease, Tooth Loss, and Cancer Risk. Epidemiol Rev 2017;39(1):49-58. PubMed DOI

Shi Q, Cai C, Xu J, Liu J, Liu H, Huo N. Is there an association between IFN-γ +874A/T polymorphism and periodontitis susceptibility?: A meta-analysis. Medicine (Baltimore) 2017;96(25):e7288. PubMed DOI

Jin SH, Guan XY, Liang WH, Bai GH, Liu JG. TLR4 polymorphism and periodontitis susceptibility: A meta-analysis. Medicine (Baltimore) 2016;95(36):e4845. PubMed DOI

Ni XB, Jia C, Yu HD, Li YQ, Zeng XT, Leng WD. Comprehensive analysis of interleukin-8 gene polymorphisms and periodontitis susceptibility. Oncotarget 2017;8(30):48996-49004. PubMed DOI

Yang ZJ, Tang XP, Lai QG, Ci JB, Yuan KF. Interleukin-8 -251A/T polymorphism and periodontitis susceptibility: a meta-analysis. Genet Mol Res 2016;21;15(4). PubMed DOI

Mlachkova A, Popova C, Doseva V. Presence of IL-8 Gene Polymorphism and IL-8 Serum Levels in Patients with Chronic Periodontitis - Literature Review. Folia Med (Plovdiv) 2020;30;62(2):253-57. PubMed DOI

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62(10):1006-12. PubMed DOI

Liukkonen J, Gürsoy UK, Könönen E, Gürsoy M, Metso J, Salminen A, Kopra E, Jauhiainen M, Mäntylä P, Buhlin K, Paju S, Sorsa T, Nieminen MS, Lokki ML, Sinisalo J, Pussinen PJ. Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype. Innate Immun 2018;24(7):439-447. PubMed DOI

Silva BRD, Cirelli T, Nepomuceno R, Theodoro LH, Orrico SRP, Cirelli JA, Barros SP, Scarel-Caminaga RM. Functional haplotype in the Interleukin8 (CXCL8) gene is associated with type 2 Diabetes Mellitus and Periodontitis in Brazilian population. Diabetes Metab Syndr 2020;14(6):1665-72. PubMed DOI

Borilova LP, Kavrikova D, Tomandlova M, Poskerova H, Rehka V, Dušek L, Izakovicova HL. Differences in Interleukin-8 Plasma Levels between Diabetic Patients and Healthy Individuals Independently on Their Periodontal Status. Int J Mol Sci 2018;19(10):3214. PubMed DOI

Sajadi M, Shahmohammadi A, Mahmazi S, Bashiri H, Bavandpour M, Yari K. Study of association between interleukin-8 - 845 T/C and + 781 C/T polymorphisms with periodontitis disease among population from Western Iran. Mol Biol Rep 2018;45(5):1263-68. PubMed DOI

Houshmand B, Hajilooi M, Rafiei A, Bidgoli M, Soheilifar S. Evaluation of IL-8 gene polymorphisms in patients with periodontitis in Hamedan, Iran. Dent Res J (Isfahan) 2012;9(4):427-32. PubMed

Borilova Linhartova P, Vokurka J, Poskerova H, Fassmann A, Izakovicova Holla L. Haplotype analysis of interleukin-8 gene polymorphisms in chronic and aggressive periodontitis. Mediators Inflamm 2013;2013:342351. PubMed DOI

Chen X, Huang J, Zhong L, Ding C. Quantitative assessment of the associations between interleukin-8 polymorphisms and periodontitis susceptibility. J Periodontol 2015;86(2):292-300. PubMed DOI

Khosropanah H, Sarvestani EK, Mahmoodi A, Golshah M. Association of IL-8 (-251 a/t) gene polymorphism with clinical parameters and chronic periodontitis. J Dent (Tehran) 2013;10(4):312-8. PubMed

Kavrikova D, Borilova Linhartova P, Lucanova S, Poskerova H, Fassmann A, Izakovicova Holla L. Chemokine Receptor 2 (CXCR2) Gene Variants and Their Association with Periodontal Bacteria in Patients with Chronic Periodontitis. Mediators Inflamm 2019;4;2019:2061868. PubMed DOI

Li G, Yue Y, Tian Y, Li JL, Wang M, Liang H, Liao P, Loo WT, Cheung MN, Chow LW. Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population. Cytokine 2012;60(2):552-60. PubMed DOI

Scarel-Caminaga RM, Kim YJ, Viana AC, Curtis KM, Corbi SC, Sogumo PM, Orrico SR, Cirelli JA. Haplotypes in the interleukin 8 gene and their association with chronic periodontitis susceptibility. Biochem Genet 2011;49(5-6):292-302. PubMed DOI

Sippert EÂ, de Oliveira e Silva C, Visentainer JE, Sell AM. Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis. PLoS One 2013;26;8(12):e83286. PubMed DOI

Andia DC, de Oliveira NF, Letra AM, Nociti FH Jr, Line SR, de Souza AP. Interleukin-8 gene promoter polymorphism (rs4073) may contribute to chronic periodontitis. J Periodontol 2011;82(6):893-9. PubMed DOI

Li ZG, Li JJ, Sun CA, Jin Y, Wu WW. Interleukin-18 promoter polymorphisms and plasma levels are associated with increased risk of periodontitis: a meta-analysis. Inflamm Res 2014;63(1):45-52. PubMed DOI

Zhang N, Xu Y, Zhang B, Zhang T, Yang H, Zhang B, Feng Z, Zhong D. Analysis of interleukin-8 gene variants reveals their relative importance as genetic susceptibility factors for chronic periodontitis in the Han population. PLoS One 2014;7;9(8):e104436. PubMed DOI

Kim YJ, Viana AC, Curtis KM, Orrico SR, Cirelli JA, Scarel-Caminaga RM. Lack of association of a functional polymorphism in the interleukin 8 gene with susceptibility to periodontitis. DNA Cell Biol 2009;28(4):185-90. DOI

Corbi SC, Anovazzi G, Finoti LS, Kim YJ, Capela MV, Secolin R, Marcaccini AM, Gerlach RF, Orrico SR, Cirelli JA, Scarel-Caminaga RM. Haplotypes of susceptibility to chronic periodontitis in the Interleukin 8 gene do not influence protein level in the gingival crevicular fluid. Arch Oral Biol 2012;57(10):1355-61. PubMed DOI

Amaya MP, Criado L, Blanco B, Gómez M, Torres O, Flórez L, González CI, Flórez O. Polymorphisms of pro-inflammatory cytokine genes and the risk for acute suppurative or chronic nonsuppurative apical periodontitis in a Colombian population. Int Endod J 2013;46(1):71-8. PubMed DOI

da Silva MK, de Carvalho ACG, Alves EHP, da Silva FRP, Pessoa LDS, Vasconcelos DFP. Genetic Factors and the Risk of Periodontitis Development: Findings from a Systematic Review Composed of 13 Studies of Meta-Analysis with 71,531 Participants. Int J Dent 2017;2017:1914073. PubMed DOI

Rusyanti Y, Widyaputra S, Maskoen AM. Periodontal tissue destruction in aggressive periodontitis: Determination of gene or environmental factors. Saudi Dent J 2019;31(2):290-99. PubMed DOI

Viana AC, Kim YJ, Curtis KM, Renzi R, Orrico SR, Cirelli JA, Scarel-Caminaga RM. Association of haplotypes in the CXCR2 gene with periodontitis in a Brazilian population. DNA Cell Biol 2010;29(4):191-200. PubMed DOI

Corbi SC, Finoti LS, Anovazzi G, Tanaka MH, Kim YJ, Secolin R, Marcaccini AM, Gerlach RF, Orrico SR, Cirelli JA, Scarel-Caminaga RM. Clinical outcomes of periodontal therapy are not influenced by the ATC/TTC haplotype in the IL8 gene. J Periodontal Res 2014;49(4):489-98. PubMed DOI

Cirelli T, Finoti LS, Corbi SCT, Anovazzi G, Nepomuceno R, Orrico SRP, Cirelli JA, Mayer MPA, Scarel-Caminaga RM. Absolute quantification of Aggregatibacter actinomycetemcomitans in patients carrying haplotypes associated with susceptibility to chronic periodontitis: multifaceted evaluation with periodontitis covariants. Pathog Dis 2017;75(7). doi: 10.1093/femspd/ftx092 PubMed DOI

Scarel-Caminaga RM, Curtis KM, Renzi R, Sogumo PM, Anovazzi G, Viana AC, Kim YJ, Orrico SR, Cirelli JA. Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis. J Negat Results Biomed 2011;10:14. PubMed DOI

Finoti LS, Corbi SC, Anovazzi G, Teixeira SR, Capela MV, Tanaka MH, Kim YJ, Orrico SR, Cirelli JA, Mayer MP, Scarel-Caminaga RM. Pathogen levels and clinical response to periodontal treatment in patients with Interleukin 8 haplotypes. Pathog Dis 2013;69(1):21-8. PubMed DOI

Kim YJ, Viana AC, Curtis KM, Orrico SR, Cirelli JA, Mendes-Junior CT, Scarel-Caminaga RM. Association of haplotypes in the IL8 gene with susceptibility to chronic periodontitis in a Brazilian population. Clin Chim Acta 2010;411(17-18):1264-8.

Sato K, Yoshimura A, Kaneko T, Ukai T, Ozaki Y, Nakamura H, Li X, Matsumura H, Hara Y, Ogata Y. A single nucleotide polymorphism in 3'-untranslated region contributes to the regulation of Toll-like receptor 4 translation. J Biol Chem 2012;287(30):25163-72. PubMed DOI

Yang ZJ, Tang XP, Lai QG, Ci JB, Yuan KF. Interleukin-8 -251A/T polymorphism and periodontitis susceptibility: a meta-analysis. Genet Mol Res 2016;21;15(4). PubMed DOI

Pigossi SC, Anovazzi G, Finoti LS, de Medeiros MC, de Souza-Moreira TM, Mayer MPA, Zanelli CF, Valentini SR, Rossa Junior C, Scarel-Caminaga RM. The ATC/TTC haplotype in the Interleukin 8 gene in response to Gram-negative bacteria: A pilot study. Arch Oral Biol 2019;107:104508. PubMed DOI

Andia DC, Letra A, Casarin RC, Casati MZ, Line SR, de Souza AP. Genetic analysis of the IL8 gene polymorphism (rs4073) in generalized aggressive periodontitis. Arch Oral Biol 2013;58(2):211-7. PubMed DOI

Papathanasiou E, Conti P, Carinci F, Lauritano D, Theoharides TC. IL-1 Superfamily Members and Periodontal Diseases. J Dent Res 2020;99(13):1425-34. PubMed DOI

Cheng R, Wu Z, Li M, Shao M, Hu T. Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review. Int J Oral Sci 2020;12(1):2. DOI

Brodzikowska A, Górska R, Kowalski J. Interleukin-1 Genotype in Periodontitis. Arch Immunol Ther Exp 2019;67:367-73. PubMed DOI

López NJ, Jara L, Valenzuela CY. Association of interleukin-1 polymorphisms with periodontal disease. J Periodontol 2005;76(2):234-43. PubMed DOI

Struch F, Dau M, Schwahn C, Biffar R, Kocher T, Meisel P. Interleukin-1 gene polymorphism, diabetes, and periodontitis: results from the Study of Health in Pomerania (SHIP). J Periodontol 2008;79(3):501-7. PubMed DOI

Kashiwagi Y, Takedachi M, Mori K, Kubota M, Yamada S, Kitamura M, Murakami S. High glucose-induced oxidative stress increases IL-8 production in human gingival epithelial cells. Oral Dis 2016;22(6):578-84. PubMed DOI

Engebretson SP, Vossughi F, Hey-Hadavi J, Emingil G, Grbic JT. The influence of diabetes on gingival crevicular fluid beta-glucuronidase and interleukin-8. J Clin Periodontol 2006;33(11):784-90. PubMed DOI

Lagdive SS, Marawar PP, Byakod G, Lagdive SB. Evaluation and comparison of interleukin-8 (IL-8) level in gingival crevicular fluid in health and severity of periodontal disease: a clinico-biochemical study. Indian J Dent Res 2013;24(2):188-92. PubMed DOI

Benakanakere M, Finoti L, Tanaka U, Grant GR, Scarel-Caminaga RM, Kinane DF. Investigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing. Sci Rep 2016:6,31180. PubMed DOI