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The association between genetic polymorphisms in matrix metalloproteinases and caries experience

Abstract

Objectives

The variation in the caries susceptibility while environmental factors are similar indicates that the effect of individual factors such as genetics on caries process and tooth development should be revealed.

The aim of this study was to evaluate the association between genetic polymorphisms in MMP13 (rs2252070) and MMP20 (rs1784418) with caries experience.

Materials and methods

A cross-sectional study was conducted on 200 subjects aged 6 to 14 years. Demographic data, data on oral health habits were obtained through the statements of guardian of the individuals, caries data was collected by clinical examination. Unstimulated whole saliva was collected to extract the genomic DNA. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between different subgroups considering caries experience. Data were analyzed using SPSS 16.0 by chi-square test and logistic regression analysis.

Results

Allele distribution of MMP13 was different between caries-affected and caries-free subjects. MMP13 A allele increased the caries risk (p=0.005, OR=1.84, 95% CI 1.20-2.82). Allele and genotype distribution of the polymorphism in MMP20 were not associated with caries experience (p>0.05).

Conclusions

It is concluded that the genetic variation in MMP13 was associated with the caries experience in selected subjects in Turkey.

Clinical relevance

The knowledge regarding association between the MMP genes and caries experience, might benefit the clinical practice, improving caries-preventive and caries-therapeutic approaches.

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References

  1. 1.

    Kilian M, Chapple ILC, Hannig M, Marsh PD, Meuric V, Pedersen AML, Tonetti MS, Wade WG, Zaura E (2016) The oral microbiome - an update for oral healthcare professionals. Br Dent J 221:657–666

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Marsh PD, Head DA, Devine DA (2015) Ecological approaches to oral biofilms: control without killing. Caries Res 1:46–54

    Article  Google Scholar 

  3. 3.

    Adler CJ, Dobney K, Weyrich LS, Kaidonis J, Walker AW, Haak W, Bradshaw CJA, Townsend G, Sołtysiak A, Alt KW, Parkhill J, Cooper A (2013) Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nat Genet 45:450–455

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Marsh PD (2010) Controlling the oral biofilm with antimicrobials. J Dent 38:11–15

    Article  Google Scholar 

  5. 5.

    Kutsch VK, Young DA (2011) New directions in the etiology of dental caries disease. J Calif Dent Assoc 39:716–721

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tannure PN, Küchler EC, Falagan-Lotsch P, Amorim LMF, Raggio Luiz R, Costa MC, Vieira AR, Granjeiro JM (2012) MMP13 polymorphism decreases risk for dental caries. Caries Res 46:401–407

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Tannure PN, Küchler EC, Lips A, Costa MC, Luiz RR, Granjeiro JM, Vieira AR (2012) Genetic variation in MMP20 contributes to higher caries experience. J Dent 40:381–386

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Vieira AR, Modesto A, Marazita ML (2014) Caries: Review of Human Genetics Research. Caries Res 48:491–506

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Slayton RL, Cooper ME, Marazita ML (2005) Tuftelin, Mutans Streptococci, and Dental Caries Susceptibility. J Dent Res 84:711–714

    PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Patir A, Seymen F, Yildirim M, Deeley K, Cooper ME, Marazita ML, Vieira AR (2008) Enamel formation genes are associated with high caries experience in Turkish children. Caries Res 42:394–400

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Lehner T, Lamb JR, Welsh KL, Batchelor RJ (1981) Association between HLA-DR antigens and helper cell activity in the control of dental caries. Nature 292:770–772

    PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

    Brancher JA, Pecharki GD, Doetzer AD et al (2011) Analysis of polymorphisms in the lactotransferrin gene promoter and dental caries. Int J Dent 2011:571726

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Wendell S, Wang X, Brown M, Cooper ME, DeSensi RS, Weyant RJ, Crout R, McNeil DW, Marazita ML (2010) Taste Genes Associated with Dental Caries. J Dent Res 89:1198–1202

    PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Kulkarni GV, Chng T, Eny KM, Nielsen D, Wessman C, El-Sohemy A (2013) Association of GLUT2 and TAS1R2 genotypes with risk for dental caries. Caries Res 47:219–225

    PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Karayasheva D, Glushkova M, Boteva E, Mitev V, Kadiyska T (2016) Association study for the role of Matrix metalloproteinases 2 and 3 gene polymorphisms in dental caries susceptibility. Arch Oral Biol 68:9–12

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 3:a005058

  17. 17.

    Hannas AR, Pereira JC, Granjeiro JM, Tjäderhane L (2007) The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand 65:1–13

    PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Raivisto T, Heikkinen A, Kovanen L, Ruokonen H, Kettunen K, Tervahartiala T, Haukka J, Sorsa T (2018) SNP Analysis of Caries and Initial Caries in Finnish Adolescents. Int J Dent 2018:1–5

    Article  Google Scholar 

  19. 19.

    Sulkala M, Pääkkönen V, Larmas M, Salo T, Tjäderhane L (2004) Matrix Metalloproteinase-13 (MMP-13, Collagenase-3) is Highly Expressed in Human Tooth Pulp. Connect Tissue Res 45:231–237

    PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Loreto C, Galanti C, Musumeci G, Rusu MC, Leonardi R (2014) Immunohistochemical analysis of matrix metalloproteinase-13 in human caries dentin. Eur J Histochem 58:2318

    PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Lee TY, Jin EJ, Choi B (2013) MMP-13 expression in coronal and radicular dentin according to caries progression -a pilot study. Tissue Eng Regen Med 10:317–321

    Article  Google Scholar 

  22. 22.

    Vasconcelos KR, Arid J, Evangelista S, Oliveira S, Dutra AL, Silva LAB, Segato RAB, Vieira AR, Nelson-Filho P, Küchler EC (2019) mmp13 contributes to dental caries associated with developmental defects of enamel. Caries Res 53(4):441–446

    PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Sulkala M, Larmas M, Sorsa T, Salo T, Tjäderhane L (2002) The Localization of Matrix Metalloproteinase-20 (MMP-20, Enamelysin) in Mature Human Teeth. J Dent Res 81:603–607

    PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Prajapati S, Tao J, Ruan Q, De Yoreo JJ, Moradian-Oldak J (2016) Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals. Biomaterials 75:260–270

    PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Bartlett JD, Beniash E, Lee DH, Smith CE (2004) Decreased Mineral Content in MMP-20 Null Mouse Enamel is Prominent During the Maturation Stage. J Dent Res 83:909–913

    PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Caterina JJ, Skobe Z, Shi J, Ding Y, Simmer JP, Birkedal-Hansen H, Bartlett JD (2002) Enamelysin (Matrix Metalloproteinase-20) deficient Mice Display an Amelogenesis Imperfecta Phenotype. J Biol Chem 277:49598–49604

    PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Chan H-C, Estrella NMRP, Milkovich RN, Kim J-W, Simmer JP, Hu JC-C (2011) Target gene analyses of 39 amelogenesis imperfecta kindreds. Eur J Oral Sci 119:311–323

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Shin M, Chavez MB, Ikeda A, Foster BL, Bartlett JD (2018) MMP20 Overexpression Disrupts Molar Ameloblast Polarity and Migration. J Dent Res 97:820–827

    PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Antunes LA, Antunes LS, Küchler EC, Lopes LB, Moura A, Bigonha RS, Abreu FV, Granjeiro JM, de Amorim LMF, Paixão ICNP (2016) Analysis of the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 genes with white spot lesions and early childhood caries. Int J Paediatr Dent 26:310–319

    PubMed  Article  PubMed Central  Google Scholar 

  30. 30.

    Filho AVA, Calixto MS, Deeley K, Santos N, Rosenblatt A, Vieira AR (2017) MMP20 rs1784418 Protects Certain Populations against Caries. Caries Res 51:46–51

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Leeman MF, Curran S, Murray GI (2002) The structure, regulation, and function of human matrix metalloproteinase-13. Crit Rev Biochem Mol Biol 37:149–166

    PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Bourd-Boittin K, Septier D, Hall R, Goldberg M, Menashi S (2004) Immunolocalization of Enamelysin (Matrix Metalloproteinase-20) in the Forming Rat Incisor. J Histochem Cytochem 52:437–445

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Sawada T, Nanci A (1995) Spatial distribution of enamel proteins and fibronectin at early stages of rat incisor tooth formation. Arch Oral Biol 40:1029–1038

    PubMed  Article  PubMed Central  Google Scholar 

  34. 34.

    Silness J, Löe H (1964) Periodontal Disease in Pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 22:121–135

    PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    World Health Organization (2013) Oral Health Surveys: Basic Methods, 5th edition. World Health Organization. https://www.who.int/oral_health/publications/9789241548649/en/. Accessed 25 August 2020

  36. 36.

    Cogulu D, Onay H, Ozdemir Y, Aslan GI, Ozkinay F, Kutukculer N et al (2015) Associations of interleukin (IL)-1β, IL-1 receptor antagonist, and IL-10 with dental caries. J Oral Sci 57:31–36

    PubMed  Article  PubMed Central  Google Scholar 

  37. 37.

    Oulis CJ, Berdouses ED (2009) Fissure sealant retention and caries development after resealing on first permanent molars of children with low, moderate and high caries risk. Eur Arch Paediatr Dent 10:211–217

    PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Wang X, Willing MC, Marazita ML, Wendell S, Warren JJ, Broffitt B, Smith B, Busch T, Lidral AC, Levy SM (2012) Genetic and environmental factors associated with dental caries in children: the Iowa Fluoride Study. Caries Res 46:177–184

    PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Ferreira SH, Béria J, Kramer PF, Feldens EG, Feldens CA (2007) Dental caries in 0- to 5-year-old Brazilian children: prevalence, severity, and associated factors. Int J Paediatr Dent 17:289–296

    PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Skinner J, Byun R, Blinkhorn A, Johnson G (2015) Sugary drink consumption and dental caries in New South Wales teenagers. Aust Dent J 60:169–175

    PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Morris-Wiman J, Burch H, Basco E (2000) Temporospatial distribution of matrix metalloproteinase and tissue inhibitors of matrix metalloproteinases during murine secondary palate morphogenesis. Anat Embryol (Berl) 202:129–141

    Article  Google Scholar 

  42. 42.

    Borilova Linhartova P, Deissova T, Kukletova M, Izakovicova Holla L (2020) Matrix metalloproteinases gene variants and dental caries in Czech children. BMC Oral Health 20:138

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Abbasoğlu Z, Tanboğa İ, Küchler EC, Deeley K, Weber M, Kaspar C, Korachi M, Vieira AR (2015) Early childhood caries is associated with genetic variants in enamel formation and immune response genes. Caries Res 49:70–77

    PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC (2006) ACE polymorphisms. Circ Res 98:1123–1133

    PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM (1996) Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem 271:13055–13060

    PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Rutter JL, Mitchell TI, Buttice G et al (1998) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 58:5321–5325

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Zhang B, Henney A, Eriksson P, Hamsten A, Watkins H, Ye S (1999) Genetic variation at the matrix metalloproteinase-9 locus on chromosome 20q12.2–13.1. Hum Genet 105:418–423

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Henney AM, Ye S, Zhang B, Jormsjo S, Whatling C, Eriksson P, Hamsten A (2000) Genetic diversity in the matrix metalloproteinase family. Effects on function and disease progression. Ann N Y Acad Sci 902:27–37

    PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Jormsjo S, Ye S, Moritz J, Walter DH, Dimmeler S, Zeiher AM, Henney A, Hamsten A, Eriksson P (2000) Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res 86:998–100

    PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Fernandez-Cadenas I, Mendioroz M, Domingues-Montanari S, Del Rio-Espinola A, Delgado P, Ruiz A, Hernandez-Guillamon M, Giralt D, Chacon P, Navarro-Sobrino M, Ribo M, Molina CA, Alvarez-Sabin J, Rosell A, Montaner J (2011) Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients. Eur J Neurol 18:826–835

    PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Sun G, Ba CL, Gao R, Liu W, Ji Q (2019) Association of IL-6, IL-8, MMP-13 gene polymorphisms with knee osteoarthritis susceptibility in the Chinese Han population. Biosci Rep 39:BSR20181346

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Shi M, Xia J, Xing H, Yang W, Xiong X, Pan W, Han S, Shang J, Zhou C, Zhou L, Yang M (2016) The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070. Sci Rep 6:27013

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Chisini LA, Cademartori MG, Conde MCM, Tovo-Rodrigues L, Correa MB (2020) Genes in the pathway of tooth mineral tissues and dental caries risk: a systematic review and meta-analysis. Clin Oral Investig 24:3723–3738

    PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Shimizu T, Ho B, Deeley K, Briseño-Ruiz J, Faraco IM Jr, Schupack BI, Brancher JA, Pecharki GD, Küchler EC, Tannure PN, Lips A, Vieira TC, Patir A, Yildirim M, Poletta FA, Mereb JC, Resick JM, Brandon CA, Orioli IM, Castilla EE, Marazita ML, Seymen F, Costa MC, Granjeiro JM, Trevilatto PC, Vieira AR (2012) Enamel formation genes influence enamel microhardness before and after cariogenic challenge. PLoS One 7:e45022

    PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Wang X, Shaffer JR, Weyant RJ, Cuenco KT, DeSensi RS, Crout R, McNeil DW, Marazita ML (2010) Genes and their effects on dental caries may differ between primary and permanent dentitions. Caries Res 44:277–284

    PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Hong EP, Park JW (2012) Sample size and statistical power calculation in genetic association studies. Genomics Inform 10:117–122

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Scherag A, Müller HH, Dempfle A, Hebebrand J, Schäfer H (2003) Data adaptive interim modification of sample sizes for candidate-gene association studies. Hum Hered 56:56–62

    PubMed  Article  PubMed Central  Google Scholar 

  58. 58.

    Pfeiffer RM, Gail MH (2003) Sample size calculations for populationand family-based case-control association studies on marker genotypes. Genet Epidemiol 25:136–148

    PubMed  Article  PubMed Central  Google Scholar 

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Acknowledgement

The authors would like to thank the participants whose contributions made this work possible. The authors also would like to thank Assoc. Prof. Timur Köse for statistical analysis.

Funding

The authors received no specific funding for this work. This study was supported by Ege University Scientific Research Projects Coordination (Grant number: 610120140006).

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Authors

Contributions

F.Ç.D wrote the first draft of the manuscript. N.E. and D.Ç. wrote the final draft of the manuscript. F.Ç.D., N.E., A.D., D.Ç., B.D. and Ö.Ç. designed the study. F.Ç.D. performed the data collection. F.Ç.D., A.D., B.D. and Ö.Ç. worked on DNA extraction and genotyping. F.Ç.D., N.E., A.D. and D.Ç. analyzed the data. All authors critically reviewed the final draft of the manuscript.

Corresponding author

Correspondence to Funda Çağırır Dindaroğlu.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Clinical Ethics Committee of Ege University School of Medicine approved the study (14-4.1/15).

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Informed consent was obtained from all individual participants included in the study.

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The authors report no conflict of interest regarding this research.

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Çağırır Dindaroğlu, F., Eronat, N., Durmaz, A. et al. The association between genetic polymorphisms in matrix metalloproteinases and caries experience. Clin Oral Invest 25, 5403–5410 (2021). https://doi.org/10.1007/s00784-021-03848-1

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Keywords

  • Dental caries
  • Matrix metalloproteinase
  • Genetic polymorphism
  • Genetic susceptibility