Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Caries Res 2017;51:209-215

Genetic Polymorphisms in DEFB1 and miRNA202 Are Involved in Salivary Human β-Defensin 1 Levels and Caries Experience in Children

Lips A.a · Antunes L.S.a, b · Antunes L.A.b · Abreu J.G.B.a · Barreiros D.c · Oliveira D.S.B.c · Batista A.C.a · Nelson-Filho P.c · Silva L.A.B.c · Silva R.A.B.c · Alves G.G.a · Küchler E.C.c

Author affiliations

aClinical Research Unit, Fluminense Federal University, Niterói, bDepartment of Specific Formation, School of Dentistry of Nova Friburgo, Fluminense Federal University, Nova Friburgo, and cDepartment of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

Corresponding Author

Dr. Erika Calvano Küchler and Dr. Gutemberg Gomes Alves

Department of Pediatric Dentistry

School of Dentistry of Ribeirão Preto, Av. do Café, S/N

Ribeirão Preto, SP 14040-904 (Brazil)

E-Mail erikacalvano@gmail.com

Do you have an account?

Login Information

Contact Information

I have read the Karger Terms and Conditions and agree.


The antimicrobial peptides human β-defensins (hBDs) are encoded by β-defensin genes (DEFBs) and are possibly involved in caries susceptibility. In this study we aimed (1) to investigate the relationship between salivary hBDs and caries and (2) to evaluate the association of genetic polymorphisms in DEFB1 and microRNA202 (miRNA202) with salivary levels of hBDs and caries experience. Two data sets were available for this study, totalizing 678 Brazilian children. Dental examination and saliva collection were performed in all included children. The salivary level for hDB1, hBD2, and hBD4 was assessed by ELISA sandwich technique in 168 children. The DNA was extracted from saliva, and polymorphisms in DEFB1 and miRNA202 were analyzed by real-time PCR. Statistical analysis was performed to investigate the associations between caries experience, hBD salivary level, genotype, and allele distribution, with an alpha of 0.05. The hBD1 level was significantly higher in caries-free children (p < 0.0001). The miRNA202 was associated with a lower level of salivary hBD1 (p < 0.05). Also, the polymorphic distribution of miRNA202 was associated with caries (p = 0.006). The polymorphisms in DEFB1 were not associated with hBD salivary level and caries experience (p > 0.05). In conclusion, our results indicate that genetic polymorphism in miRNA202 is involved in hBD1 salivary level as well as caries experience in children.

© 2017 S. Karger AG, Basel


  1. Anjomshoaa I, Briseño-Ruiz J, Deeley K, Poletta FA, Mereb JC, et al: Aquaporin 5 Interacts with fluoride and possibly protects against caries. PLoS One 2015;10:e0143068.
  2. Antunes LA, Antunes LS, Küchler EC, Lopes LB, Moura A, et al: 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 2016;26:310-319.
  3. Azevedo LF, Pecharki GD, Brancher JA, Cordeiro CA Jr, Medeiros KG, et al: Analysis of the association between lactotransferrin (LTF) gene polymorphism and dental caries. Appl Oral Sci 2010;18:166-170.
  4. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD: MicroRNAs: new regulators of immune cell development and function. Nat Immunol 2008;9:839-845.
  5. 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 Prev Dent 2008;26:18-21.
  6. Betel D, Koppal A, Agius P, Sander C, Leslie C: mirSVR predicted target site scoring method: comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 2010;11:R90.
  7. Bonass WA, High AS, Owen PJ, Devine DA: Expression of beta-defensin genes by human salivary glands. Oral Microbiol Immunol 1999;14:371-374.
  8. Cai X, Hagedorn CH, Cullen BR: Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004;10:1957-1966.
  9. Dale BA, Kimball JR, Krisanaprakornkit S, Roberts F, Robino-vitch M, O'Neal R, Valore EV, Ganz T, Anderson GM, Weinberg A: Localized antimicrobial peptide expression in human gingiva. J Periodontal Res 2001;36:285-294.
  10. Dunsche A, Acil Y, Dommisch H, Siebert R, Schroder JM, Jepsen S: The novel human β-defensin-3 is widely expressed in oral tissues. Eur J Oral Sci 2002;110:121-124.
  11. Fine DH, Toruner GA, Velliyagounder K, Sampathkumar V, Godboley D, Furgang D: A lactotransferrin single nucleotide polymorphism demonstrates biological activity that can reduce susceptibility to caries. Infect Immun 2013;81:1596-1605.
  12. Fisher-Owens SA, Gansky SA, Platt LJ, Weintraub JA, Soobader MJ, Bramlett MD, Newacheck PW: Influences on children's oral health: a conceptual model. Pediatrics 2007;120:e510-e520.
  13. Hoffman AE, Liu R, Fu A, Zheng T, Slack F, Zhu Y: Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis. Cancer Epidemiol Biomarkers Prev 2013;7:327-336.
  14. Joly S, Maze C, McCray PB, Guthmiller JM: Human-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol 2004;42:1024-1029.
  15. Kang SW, Yoon I, Lee HW, Cho J: Association between AMELX polymorphisms and dental caries in Koreans. Oral Dis 2011;17:399-406.
  16. Krasone K, Lāce B, Akota I, Care R, Deeley K, Küchler EC, Vieira AR: Genetic variation in the promoter region of beta-defensin 1 (DEFB 1) is associated with high caries experience in children born with cleft lip and palate. Acta Odontol Scand 2014;72:235-240.
  17. Küchler EC, Tannure PN, Falagan-Lotsch P, Lopes TS, Granjeiro JM, Amorim LM: Buccal cells DNA extraction to obtain high quality human genomic DNA suitable for polymorphism genotyping by PCR-RFLP and real-time PCR. J Appl Oral Sci 2012;20:467-471.
  18. Navazesh M, Christensen CM: A comparison of whole mouth resting and stimulated salivary measurement procedures. J Dent Res1982;61:1158-1162.
  19. Nishimura E, Eto A, Kato M, Hashizume S, Imai S, Nisizawa T, Hanada N: Oral streptococci exhibit diverse susceptibility to human β-defensin-2: antimicrobial effects of hBD-2 on oral streptococci. Curr Microbiol 2004;48:85-87.
  20. Ozturk A, Famili P, Vieira AR: The antimicrobial peptide DEFB1 is associated with caries. J Dent Res 2010;89:631-636.
  21. Park K, Lee S, Lee YM: Sphingolipids and antimicrobial peptides: function and roles in atopic dermatitis. Biomol Ther 2013;21:251-257.
  22. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SD: Color and genomic ancestry in Brazilians. Proc Natl Acad Sci USA 2003;100:177-182.
  23. Patir A, Seymen F, Yildirim M, Deeley K, Cooper ME, Marazita ML, Vieira AR: Enamel formation genes are associated with high caries experience in Turkish children. Caries Res 2008;42:394-400.
  24. Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C: The global burden of oral diseases and risks to oral health. Bull World Health Organ 2005;83:661-669.
    External Resources
  25. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, et al: Requirement of bic/microRNA-155 for normal immune function. Science 2007;316:608-611.
  26. Saha R, Sood PB, Sandhu M, Diwaker A, Upadhyaye S: Association of amelogenin with high caries experience in Indian children. J Clin Pediatr Dent 2015;39:458-461.
  27. Sahasrabudhe KS, Kimball JR, Morton TH, Weinberg A, Dale BA: Expression of the antimicrobial peptide, human β-defensin 1, in duct cells of minor salivary glands and detection in saliva. J Dent Res 2000;79:1669-1674.
  28. Sengul F, Kilic M, Gurbuz T, Tasdemir S: Carbonic anhydrase VI gene polymorphism rs2274327 relationship between salivary parameters and dental-oral health status in children. Biochem Genet 2016;54:467-475.
  29. Shimizu T, Ho B, Deeley K, Briseño-Ruiz J, Faraco IM Jr, Schupack BI, et al: Enamel formation genes influence enamel microhardness before and after cariogenic challenge. PLoS One 2012;7:e45022.
  30. Silness J, Löe H: Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 1964;22:121-135.
  31. Sonkoly E, Ståhle M, Pivarcsi A: MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol 2008;18:131-140.
  32. Tannure PN, Küchler EC, Lips A, Costa Mde C, Luiz RR, Granjeiro JM, Vieira AR: Genetic variation in MMP20 contributes to higher caries experience. J Dent 2012;40:381-386.
  33. Tao R, Jurevic RJ, Coulton KK, Tsutsui MT, Roberts MC, Kimball JR, Wells N, Berndt J, Dale BA: Salivary antimicrobial peptide expression and dental caries experience in children. Antimicrob Agents Chemother 2005;49:3883-3888.
  34. Valarini N, Maciel SM, Moura SK, Poli-Frederico RC: Association of dental caries with HLA Class II allele in Brazilian adolescents. Caries Res 2012;46:530-535.
  35. Vieira AR, Modesto A, Marazita ML: Caries: review of human genetics research. Caries Res 2014;48:491-506.
  36. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ: Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 2004;22:181-215.
  37. Yildiz G, Ermis RB, Calapoglu NS, Celik EU, Türel GY: Gene-environment Interactions in the etiology of dental caries. J Dent Res 2016;95:74-79.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 12, 2016
Accepted: January 30, 2017
Published online: March 25, 2017

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 5

ISSN: 0008-6568 (Print)
eISSN: 1421-976X (Online)

For additional information: https://www.karger.com/CRE