The Role of Genetic Factors in the Outbreak Mechanism of Dental Caries

Objective: The aim of the present study was to investigate the relationships between cariogenic bacterial infection and single nucleotide polymorphisms (SNPs) in candidate genes associated with dental caries, and to explore the factors related to caries in children.

Study design: Children aged 3 to 11 years were selected. Detection of cariogenic bacteria (Streptococcus mutans, Streptococcus oralis, Streptococcus sobrinus and Lactobacillus) from the plaque of each patient, and SNP analyses of five candidate genes (MBL2, TAS2R38, GLUT2, MMP13 and CA6) were performed using DNA isolated from buccal mucosal cells. The dental caries experience in primary and permanent teeth was determined using the decayed, missing and filled teeth (DMFT) index, and the effects of the observed factors on the DMFT value were analyzed by multiple regression analysis. Results: The results of the multiple regression analysis showed that the DMFT value significantly increased in the presence of S. mutans or S. sobrinus (p < 0.001), while the dmft/DMFT value decreased in the presence of nucleobase C in MBL2 (p < 0.05). Conclusion: These results suggest that the MBL2 gene is related to the pathogenesis of dental caries.

Caries risk, children, cariogenic bacteria, MBL2

1. Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev 50: 353-380, 1986.

2. Werneck RI, Mira MT, Trevilatto PC. A critical review: an overview of genetic influence on dental caries. Oral Dis 16: 613–623, 2010.

3. Wright JT. Defining the Contribution of Genetics in the Etiology of Dental Caries. J Dent Res 89: 1173-1174, 2010.

4. Bagherian A, Nematollahi H, Afshari JT, Moheghi N. Comparison of allele frequency for HLA-DR and HLA-DQ between patients with ECC and caries-free children. J Indian Soc Pedod Prevent Dent 26: 18-21, 2008.

5. Ranade K, Chang MS, Ting CT, Pei D, Hsiao CF, Olivier M, Pesich R, Hebert J, Chen YDI, Dzau VJ, Curb D, Olshen R, Risch N, Cox DR, Botstein D. High-Throughput Genotyping with Single Nucleotide Poly-morphisms. Genome Res 11: 1262-1268, 2001.

6. Ezekowitz RA. Role of the Mannose-Binding Lectin in Innate Immunity. J Infect Dis 187 (Suppl 2): S335–9, 2003.

7. Werneck RI, Lázaro FP, Cobat A, Grant AV, Xavier MB, Abel L, Alcaïs A, Trevilatto PC, Mira MT. A Major Gene Effect Controls Resistance to Caries. J Dent Res 90: 735-739, 2011.

8. Wang X, Willing MC, Marazita ML, Wendell S, Warren JJ, Broffitt B, Smith B, Busch T, Lidral AC, Levy SM. Genetic and Environmental Factors Associated with Dental Caries in Children: The Iowa Fluoride Study. Caries Res 46: 177–184, 2012.

9. Garred P. Mannose-binding lectin genetics: from A to Z. Biochem Soc Trans 36: 61–1466, 2008.

10. Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun 7: 85–94, 2006.

11. Olszowski T, Adler G, Janiszewska-Olszowska J, Safranow K, Kaczmarczyk M. Oral Dis 18: 389–395, 2012.

12. Wendell S, Wang X, Brown M, Cooper ME, DeSensi RS, Weyan RJ, Crou R, D.W McNeil DW, Marazita ML. Taste Genes Associated with Dental Caries. J Dent Res 89: 1198-1202, 2010.

13. Eny KM, Wolever TMS, Fontaine-Bisson B, El-Sohemy A. Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations. Physiol Genomics 33: 355–360, 2008.

14. Kulkarni GV, Chng T, Eny KM, Nielsen D, Wessman C, El-Sohemy A. Association of GLUT2 and TAS1R2 Genotypes with Risk for Dental Caries. Caries Res 47: 219–225, 2013.

15. Sorsa T, Tjäderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 10. 311–318, 2004.

16. Sulkala M, Pääkkönen V, Larmas M, Salo T, Tjäderhane L. Matrix metal-loproteinase-13 (MMP-13, collagenase-3) is highly expressed in human tooth pulp. Connect Tissue Res 45: 231-7, 2004.

17. Yamagiwa H, Tokunaga K, Hayami T, Hatano H, Uchida M, Endo N, Takahashi HE. Expression of Metalloproteinase-13 (Collagenase-3) Is Induced During Fracture Healing in Mice. Bone 25: 197–203, 1999.

18. Tannure PN, Küchler EC, Falagan-Lotsch P, Amorim LMF, Luiz RR, Costa MC, Vieira AR, Granjeiro JM. MMP13 Polymorphism Decreases Risk for Dental Caries. Caries Res 46: 401–407, 2012.

19. Peres RCR, Camargo G, Mofatto LS, Cortellazzi KL, Santos MCLG, Santos MN, Bergamaschi CC, Line SRP. Association of polymorphisms in the carbonic anhydrase 6 gene with salivary buffer capacity, dental plaque pH, and caries index in children aged 7–9 years. Pharmacog-enomics J 10: 114–119, 2010.

20. Aidar M, Marques MR, Valjakka J, Mononen N, Lehtimäki T, Parkkila S, Souza de AP, Line SRP. Effect of Genetic Polymorphisms in CA6 Gene on the Expression and Catalytic Activity of Human Salivary Carbonic Anhydrase VI. Caries Res 47: 414–420, 2013.

21. Shimomura-Kuroki J, Yamashita-Matsuda K, Miyagawa Y, Shimooka S. Prevalence of Cariogenic and Periodontopathic Bacteria in Japanese Children in the Primary and Mixed Dentitions. J Clin Pediatr Dent 36: 31–36, 2011.

22. WHO. Dentition status and treatment needs. In: Oral health surveys: basic methods, 4th ed. Geneva; World Health Organization, 40–47, 1997.

23. Shimomura-Kuroki J, Yamashita K, Shimooka S. Tannerella forsythia and the HLA-DQB1 allele are associated with susceptibility to periodontal disease in Japanese adolescents. Odontology 97: 32-37, 2009.

24. Hamada S, Slade HD. Biology, immunology, and cariogenicity of Strep-tococcus mutans. Microbiol Rev 44: 331-384, 1980.

25. Fujiwara T, Sasada E, Mima N, Ooshima T. Caries prevalence and sali-vary mutans streptococci in 0-2-year-old children of Japan. Community Dent Oral Epidemiol 19: 151-154, 1991.

26. Hirose H, Hirose K, Isogai E, Miura H, Ueda I. Close association between Streptococcus sobrinus in the saliva of young children and smooth surface caries increment. Caries Res 27: 292-297, 1993.

27. Belstrøm D, Fiehn NE, Nielsen CH, Klepac-Ceraj V, Paster BJ, Twetman S, Holmstrup P. Differentiation of salivary bacterial profiles of subjects with periodontitis and dental caries. J Oral Microbiol 7: 27429, 2015.

28. Soete de M, Dekeyser C, Pauwels M, Teughels W, Steenberghe van D, Quirynen M. Increase in Cariogenic Bacteria after Initial Periodontal Therapy. J Dent Res 84: 48-53, 2005.

29. Singh S, Sharma A, Sood PB, Sood A, Zaidi I, Sinha A. Saliva as a predic-tion tool for dental caries: An in vivo study. J Oral Biol Craniofac Res 5: 59- 64, 2015.

30. Mori F, Hiraishi N, Otsuki M, Tagami J. Effect of mastication on flow and properties of saliva. Asian Pac J Dent 12: 1-5, 2012.