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Genes in the pathway of tooth mineral tissues and dental caries risk: a systematic review and meta-analysis

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Abstract

Objectives

To perform a systematic review of the literature, investigating the influence of tooth mineral tissues genes on dental caries.

Materials and methods

Five databases were searched. Only human studies with cross-sectional, longitudinal, and case-control design were included. Meta-analysis was performed for each polymorphism, providing allele and genotype estimates. A meta-analysis was performed, pooling several polymorphisms for each gene. A Funnel Plot and Egger’s test were also performed.

Results

A total of 1124 records were found. Of these, 25 papers were included in the systematic review and 18 in the meta-analysis. Most of the studies (52%) were of medium quality. With regard to the allele analysis, the T allele of rs134136 (TFIP11) (OR 1.51; 95%CI 1.02–2.22) showed an association with high experience of caries and the summarization of polymorphisms investigated in the TFIP11 gene, after exclusion of SNP linkage disequilibrium, showed an association with caries experience (OR 1.64; 95%CI 1.08–2.50). An analysis of the homozygous genotype did not show any significant association. The pooled SNPs of AMBN showed associations with caries (OR 0.45; 95%CI 0.29–0.72). The pooled polymorphisms of AMELX were associated with caries experience (OR 1.78; 95%CI 1.23–2.56). In the analysis of the homozygous genotype, no SNP showed a significant association. Egger’s test showed no significant publication bias for all models (p > 0.05).

Conclusion

The present findings showed that the genes TFIP11, AMBN, and AMELX play an important role in dental caries.

Clinical relevance

Several single nucleotide polymorphisms related to the genes in the formation of tooth mineral are linked to the occurrence of dental caries, and these genes have proved to be important for an explanation of differences in the risk of dental caries.

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References

  1. Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W (2015) Global burden of untreated caries: a systematic review and metaregression. J Dent Res 94:650–658. https://doi.org/10.1177/0022034515573272

    Article  PubMed  Google Scholar 

  2. Ferreira MC, Ramos-Jorge ML, Marques LS, Ferreira FO (2017) Dental caries and quality of life of preschool children: discriminant validity of the ECOHIS. Braz Oral Res 31:e24. https://doi.org/10.1590/1807-3107BOR-2017.vol31.0024

    Article  PubMed  Google Scholar 

  3. Maltz M, Alves LS, Zenkner J (2017) Biofilm control and oral hygiene practices. Monogr Oral Sci 26:76–82. https://doi.org/10.1159/000479348

    Article  PubMed  Google Scholar 

  4. van Loveren C, Duggal MS (2001) The role of diet in caries prevention. Int Dent J 51:399–406

    Article  PubMed  Google Scholar 

  5. Dutra ER, Chisini LA, Cademartori MG, Oliveira LJC, Demarco FF, Correa MB (2018) Accuracy of partial protocol to assess prevalence and factors associated with dental caries in schoolchildren between 8-12 years of age. Cad Saude Publica 34:e00077217. https://doi.org/10.1590/0102-311x00077217

    Article  PubMed  Google Scholar 

  6. Chisini LA, Collares K, Cademartori MG, de Oliveira LJC, Conde MCM, Demarco FF, Corrêa MB (2018) Restorations in primary teeth: a systematic review on survival and reasons for failures. Int J Paediatr Dent 28:123–139. https://doi.org/10.1111/ipd.12346

    Article  PubMed  Google Scholar 

  7. Chisini LA, Noronha TG, Ramos EC, Santos-Junior RB, Sampaio KH, Faria-e-Silva AL, Corrêa MB (2018) Does the skin color of patients influence the treatment decision-making of dentists? A randomized questionnaire-based study. Clin Oral Investig 23:1023–1030. https://doi.org/10.1007/s00784-018-2526-7

    Article  PubMed  Google Scholar 

  8. Slade GD, Sanders AE, Do L, Roberts-Thomson K, Spencer AJ (2013) Effects of fluoridated drinking water on dental caries in Australian adults. J Dent Res 92:376–382. https://doi.org/10.1177/0022034513481190

    Article  PubMed  Google Scholar 

  9. Vieira AR, Modesto A, Marazita ML (2014) Caries: review of human genetics research. Caries Res 48:491–506. https://doi.org/10.1159/000358333

    Article  PubMed  Google Scholar 

  10. Deeley K et al (2008) Possible association of amelogenin to high caries experience in a Guatemalan-Mayan population. Caries Res 42:8–13. https://doi.org/10.1159/000111744

    Article  PubMed  Google Scholar 

  11. Shaffer JR et al (2013) GWAS of dental caries patterns in the permanent dentition. J Dent Res 92:38–44. https://doi.org/10.1177/0022034512463579

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zeng Z, Shaffer JR, Wang X, Feingold E, Weeks DE, Lee M, Cuenco KT, Wendell SK, Weyant RJ, Crout R, McNeil D, Marazita ML (2013) Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. J Dent Res 92:432–437. https://doi.org/10.1177/0022034513481976

    Article  PubMed  PubMed Central  Google Scholar 

  13. Haworth S et al (2018) Consortium-based genome-wide meta-analysis for childhood dental caries traits. Hum Mol Genet 27:3113–3127. https://doi.org/10.1093/hmg/ddy237

    Article  PubMed  PubMed Central  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang J, Yu K (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280:1690–1691

    Article  PubMed  Google Scholar 

  16. Chisini LA et al (2019) Is the use of Cannabis associated with periodontitis? A systematic review and meta-analysis. J Periodontal Res. https://doi.org/10.1111/jre.12639

  17. Dorak MT (2017) Genetic association studies: background, conduct, analysis, interpretation. Garland Science, Taylor & Francis Group, New York

    Google Scholar 

  18. Palmer T, Peters J, Sutton A, Moreno S (2008) Contour-enhanced funnel plots for meta-analysis. Stata J 8:242

    Article  Google Scholar 

  19. Kuchler EC et al (2017) Genes involved in the enamel development are associated with calcium and phosphorus level in saliva. Caries Res 51:225–230. https://doi.org/10.1159/000450764

    Article  PubMed  Google Scholar 

  20. Saha R et al (2015) Association of amelogenin with high caries experience in Indian children. The Journal of clinical pediatric dentistry 39:458–461. https://doi.org/10.17796/1053-4628-39.5.458

    Article  PubMed  Google Scholar 

  21. Lu Y, Papagerakis P, Yamakoshi Y, Hu JC, Bartlett JD, Simmer JP (2008) Functions of KLK4 and MMP-20 in dental enamel formation. Biol Chem 389:695–700. https://doi.org/10.1515/BC.2008.080

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chaussain C, Bouazza N, Gasse B, Laffont AG, Opsahl Vital S, Davit-Béal T, Moulis E, Chabadel O, Hennequin M, Courson F, Droz D, Vaysse F, Laboux O, Tassery H, Carel JC, Alcais A, Treluyer JM, Beldjord C, Sire JY (2014) Dental caries and enamelin haplotype. J Dent Res 93:360–365. https://doi.org/10.1177/0022034514522060

    Article  PubMed  Google Scholar 

  23. Gasse B, Grabar S, Lafont AG, Quinquis L, Opsahl Vital S, Davit-Béal T, Moulis E, Chabadel O, Hennequin M, Courson F, Droz D, Vaysse F, Laboux O, Tassery H, al-Hashimi N, Boillot A, Carel JC, Treluyer JM, Jeanpierre M, Beldjord C, Sire JY, Chaussain C (2013) Common SNPs of AmelogeninX (AMELX) and dental caries susceptibility. J Dent Res 92:418–424. https://doi.org/10.1177/0022034513482941

    Article  PubMed  Google Scholar 

  24. Gerreth K, Zaorska K, Zabel M, Borysewicz-Lewicka M, Nowicki M (2016) Association of ENAM gene single nucleotide polymorphisms with dental caries in Polish children. Clin Oral Investig 20:631–636. https://doi.org/10.1007/s00784-016-1743-1

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gerreth K et al (2017) Chosen single nucleotide polymorphisms (SNPs) of enamel formation genes and dental caries in a population of Polish children. Adv Clin Exp Med 26:899–905. https://doi.org/10.17219/acem/63024

    Article  PubMed  Google Scholar 

  26. Slayton RL, Cooper ME, Marazita ML (2005) Tuftelin, mutans streptococci, and dental caries susceptibility. J Dent Res 84:711–714. https://doi.org/10.1177/154405910508400805

    Article  PubMed  Google Scholar 

  27. 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. https://doi.org/10.1159/000154785

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kang SW, Yoon I, Lee HW, Cho J (2011) Association between AMELX polymorphisms and dental caries in Koreans. Oral Dis 17:399–406. https://doi.org/10.1111/j.1601-0825.2010.01766.x

    Article  PubMed  Google Scholar 

  29. Olszowski T, Adler G, Janiszewska-Olszowska J, Safranow K, Kaczmarczyk M (2012) MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children. Oral Dis 18:389–395. https://doi.org/10.1111/j.1601-0825.2011.01887.x

    Article  PubMed  Google Scholar 

  30. 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. https://doi.org/10.1371/journal.pone.0045022

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tannure PN, Küchler EC, Lips A, Costa Mde C, Luiz RR, Granjeiro JM, Vieira AR (2012) Genetic variation in MMP20 contributes to higher caries experience. J Dent 40:381–386. https://doi.org/10.1016/j.jdent.2012.01.015

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tannure PN, Küchler EC, Falagan-Lotsch P, Amorim LM, Raggio Luiz R, Costa MC, Vieira AR, Granjeiro JM (2012) MMP13 polymorphism decreases risk for dental caries. Caries Res 46:401–407. https://doi.org/10.1159/000339379

    Article  PubMed  Google Scholar 

  33. 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. https://doi.org/10.1159/000337282

    Article  PubMed  Google Scholar 

  34. Jeremias F, Koruyucu M, Küchler EC, Bayram M, Tuna EB, Deeley K, Pierri RA, Souza JF, Fragelli CM, Paschoal MA, Gencay K, Seymen F, Caminaga RM, dos Santos-Pinto L, Vieira AR (2013) Genes expressed in dental enamel development are associated with molar-incisor hypomineralization. Arch Oral Biol 58:1434–1442. https://doi.org/10.1016/j.archoralbio.2013.05.005

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ergoz N et al (2014) Genetic variation in Ameloblastin is associated with caries in asthmatic children. Eur Arch Paediatr Dent 15:211–216. https://doi.org/10.1007/s40368-013-0096-6

    Article  PubMed  Google Scholar 

  36. Ohta M, Nishimura H, Asada Y (2014) Association of DLX3 gene polymorphism and dental caries susceptibility in Japanese children. Arch Oral Biol 60:55–61. https://doi.org/10.1016/j.archoralbio.2014.08.020

    Article  Google Scholar 

  37. Abbasoglu Z et al (2015) Early childhood caries is associated with genetic variants in enamel formation and immune response genes. Caries Res 49:70–77. https://doi.org/10.1159/000362825

    Article  PubMed  Google Scholar 

  38. Romanos HF et al (2015) BMP2 is associated with caries experience in primary teeth. Caries Res 49:425–433. https://doi.org/10.1159/000371715

    Article  PubMed  Google Scholar 

  39. Shaffer JR, Carlson JC, Stanley BO, Feingold E, Cooper M, Vanyukov MM, Maher BS, Slayton RL, Willing MC, Reis SE, McNeil D, Crout RJ, Weyant RJ, Levy SM, Vieira AR, Marazita ML (2015) Effects of enamel matrix genes on dental caries are moderated by fluoride exposures. Hum Genet 134:159–167. https://doi.org/10.1007/s00439-014-1504-7

    Article  PubMed  Google Scholar 

  40. Antunes LA, Antunes LS, Küchler EC, Lopes LB, Moura A, Bigonha RS, Abreu FV, Granjeiro JM, de Amorim LM, Paixão IC (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. https://doi.org/10.1111/ipd.12202

    Article  PubMed  Google Scholar 

  41. Yildiz G, Ermis RB, Calapoglu NS, Celik EU, Türel GY (2016) Gene-environment Interactions in the etiology of dental caries. J Dent Res 95:74–79. https://doi.org/10.1177/0022034515605281

    Article  PubMed  Google Scholar 

  42. Cavallari T, Tetu Moyses S, Moyses SJ, Iani Werneck R (2017) KLK4 gene and dental decay: replication in a South Brazilian Population. Caries Res 51:240–243. https://doi.org/10.1159/000464450

    Article  PubMed  Google Scholar 

  43. Filho AV, Calixto MS, Deeley K, Santos N, Rosenblatt A, Vieira AR (2017) MMP20 rs1784418 protects certain populations against caries. Caries Res 51:46–51. https://doi.org/10.1159/000452345

    Article  PubMed  Google Scholar 

  44. Borilova Linhartova P, Deissova T, Musilova K, Zackova L, Kukletova M, Kukla L, Izakovicova Holla L (2017) Lack of association between ENAM gene polymorphism and dental caries in primary and permanent teeth in Czech children. Clin Oral Investig 22:1873–1877. https://doi.org/10.1007/s00784-017-2280-2

    Article  PubMed  Google Scholar 

  45. Wang M, Qin M, Xia B (2017) The association of enamelin, lactoferrin, and tumour necrosis factor alpha gene polymorphisms with high caries susceptibility in Chinese children under 4 years old. Arch Oral Biol 80:75–81. https://doi.org/10.1016/j.archoralbio.2017.03.023

    Article  PubMed  Google Scholar 

  46. Weber M, Bogstad Søvik J, Mulic A, Deeley K, Tveit AB, Forella J, Shirey N, Vieira AR (2018) Redefining the phenotype of dental caries. Caries Res 52:263–271. https://doi.org/10.1159/000481414

    Article  PubMed  Google Scholar 

  47. Lacruz RS, Habelitz S, Wright JT, Paine ML (2017) Dental enamel formation and implications for oral health and disease. Physiol Rev 97:939–993. https://doi.org/10.1152/physrev.00030.2016

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lu T, Li M, Xu X, Xiong J, Huang C, Zhang X, Hu A, Peng L, Cai D, Zhang L, Wu B, Xiong F (2018) Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders. Int J Oral Sci 10:26. https://doi.org/10.1038/s41368-018-0027-9

    Article  PubMed  PubMed Central  Google Scholar 

  49. Poulter JA, Murillo G, Brookes SJ, Smith CE, Parry DA, Silva S, Kirkham J, Inglehearn CF, Mighell AJ (2014) Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum Mol Genet 23:5317–5324. https://doi.org/10.1093/hmg/ddu247

    Article  PubMed  PubMed Central  Google Scholar 

  50. Grinde KE et al (2019) Generalizing polygenic risk scores from Europeans to Hispanics/Latinos. Genet Epidemiol 43:50–62. https://doi.org/10.1002/gepi.22166

    Article  PubMed  Google Scholar 

  51. Shaffer JR, Wang X, Feingold E, Lee M, Begum F, Weeks DE, Cuenco KT, Barmada MM, Wendell SK, Crosslin DR, Laurie CC, Doheny KF, Pugh EW, Zhang Q, Feenstra B, Geller F, Boyd HA, Zhang H, Melbye M, Murray JC, Weyant RJ, Crout R, McNeil D, Levy SM, Slayton RL, Willing MC, Broffitt B, Vieira AR, Marazita ML (2011) Genome-wide association scan for childhood caries implicates novel genes. J Dent Res 90:1457–1462. https://doi.org/10.1177/0022034511422910

    Article  PubMed  PubMed Central  Google Scholar 

  52. Wang X, Shaffer JR, Zeng Z, Begum F, Vieira AR, Noel J, Anjomshoaa I, Cuenco KT, Lee MK, Beck J, Boerwinkle E, Cornelis MC, Hu FB, Crosslin DR, Laurie CC, Nelson SC, Doheny KF, Pugh EW, Polk DE, Weyant RJ, Crout R, McNeil D, Weeks DE, Feingold E, Marazita ML (2012) Genome-wide association scan of dental caries in the permanent dentition. BMC Oral Health 12:57. https://doi.org/10.1186/1472-6831-12-57

    Article  PubMed  PubMed Central  Google Scholar 

  53. Clayton DG (2009) Sex chromosomes and genetic association studies. Genome Med 1:110. https://doi.org/10.1186/gm110

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was conducted in a Graduate Program supported by CAPES, Brazil.

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Correspondence to Marcos Britto Correa.

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Supplementary material S1.

Main characteristics of studies included in this systematic review (DOCX 77 kb)

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Chisini, L.A., Cademartori, M.G., Conde, M.C.M. et al. Genes in the pathway of tooth mineral tissues and dental caries risk: a systematic review and meta-analysis. Clin Oral Invest 24, 3723–3738 (2020). https://doi.org/10.1007/s00784-019-03146-x

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