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Vol. 42, No. 5, 2008
Issue release date: September 2008
Free Access
Caries Res 2008;42:394–400
(DOI:10.1159/000154785)

Enamel Formation Genes Are Associated with High Caries Experience in Turkish Children

Patir A.a · Seymen F.a · Yildirim M.a · Deeley K.b · Cooper M.E.b · Marazita M.L.b, d, e · Vieira A.R.b, c, d
aDepartment of Pedodontics, Istanbul University, Istanbul, Turkey; bDepartment of Oral Biology and Center for Craniofacial and Dental Genetics and cDepartment of Pediatric Dentistry, School of Dental Medicine, dDepartment of Human Genetics, Graduate School of Public Health, and eDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pa., USA
email Corresponding Author

Abstract

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes and their interaction with Streptococcus mutans levels may contribute to caries. For the present study, we used DNA samples collected from 173 unrelated children from Istanbul: 91 children with 4 or more affected tooth surfaces and 82 caries-free children. Six single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Regression analysis was used for the evaluation of individual gene effects, environmental effects and gene-environment interactions. Overrepresentation of the C allele of the amelogenin marker was seen in cases with dmft scores higher than 8 (p = 0.01) when compared to controls. Also, overrepresentation of the T allele of the ameloblastin marker was seen in cases with dmfs scores higher than 10 (p = 0.05) when compared to controls. In addition, the CT genotype of the tuftelin rs3790506 marker was overrepresented in cases with dmft scores higher than 5 (p = 0.05) and dmfs scores higher than 6 (p = 0.05) compared to controls. The best-fitting model showed that dmfs is increased when the following factors are present: (1) females and both the anterior and posterior teeth are affected simultaneously, (2) when the T allele of the tuftelin rs3790506 is involved, and (3) the C allele of the amelogenin rs17878486 is involved. Our study provides support that genes involved in enamel formation modify caries susceptibility in humans.


 goto top of outline Key Words

  • Ameloblastin
  • Amelogenin
  • Enamelin
  • Tuftelin
  • Tuftelin interacting protein 11

 goto top of outline Abstract

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes and their interaction with Streptococcus mutans levels may contribute to caries. For the present study, we used DNA samples collected from 173 unrelated children from Istanbul: 91 children with 4 or more affected tooth surfaces and 82 caries-free children. Six single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Regression analysis was used for the evaluation of individual gene effects, environmental effects and gene-environment interactions. Overrepresentation of the C allele of the amelogenin marker was seen in cases with dmft scores higher than 8 (p = 0.01) when compared to controls. Also, overrepresentation of the T allele of the ameloblastin marker was seen in cases with dmfs scores higher than 10 (p = 0.05) when compared to controls. In addition, the CT genotype of the tuftelin rs3790506 marker was overrepresented in cases with dmft scores higher than 5 (p = 0.05) and dmfs scores higher than 6 (p = 0.05) compared to controls. The best-fitting model showed that dmfs is increased when the following factors are present: (1) females and both the anterior and posterior teeth are affected simultaneously, (2) when the T allele of the tuftelin rs3790506 is involved, and (3) the C allele of the amelogenin rs17878486 is involved. Our study provides support that genes involved in enamel formation modify caries susceptibility in humans.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
  1. Alvesalo L: Sex chromosomes and human growth: a dental approach. Hum Genet 1997;101:1–5.
  2. Ayad M, van Wuyckhuyse BC, Minaguchi K, Raubertas RF, Bedi GF, Billings RJ, Bowen WH, Tabak LA: The association of basic proline-rich peptides from human parotid gland secretions with caries experience. J Dent Res 2000;79:976–982.
  3. Declerck D, Leroy R, Martens L, Lesaffre E, Garcia-Zattera MJ, van den Broucke S, Debyser M, Hoppenbrouwers K: Factors associated with prevalence and severity of caries experience in preschool children. Community Dent Oral Epidemiol 2008;36:168–178.
  4. Deeley K, Letra A, Rose EK, Brandon CA, Resick JM, Marazita ML, Vieira AR: Possible association of amelogenin to high caries experience in a Guatemalan-Mayan population. Caries Res 2008;42:8–13.
  5. Hu JCC, Chun YHP, Al Hazzazzi T, Simmer JP: Enamel formation and amelogenesis imperfecta. Cell Tissues Organs 2007;186:78–85.
  6. Hunt HR, Hoppert CA, Erwin WG: Inheritance of susceptibility to caries in albino rats (Mus norvegicus). J Dent Res 1944;23:385–401.
  7. Ioannidis JPA, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG: Replication validity of genetic association studies. Nat Genet 2001;29:306–309.
  8. Klein H: The family and dental disease. IV. Dental disease (DMF) experiences in parents and offspring. J Am Dent Assoc 1946;33:735–743.

    External Resources

  9. Klein H, Palmer CE: Dental caries in brothers and sisters of immune and susceptible children. Milbank Mem Fund Q 1940;18:67–82.

    External Resources

  10. Krebsbach PH, Lee SK, Matsuli Y, Kozak CA, Yamada KM, Yamada Y: Full-length sequence, localization, and chromosomal mapping of ameloblastin: a novel tooth-specific gene. J Biol Chem 1996;271:4431–4435.
  11. Lukacs JR, Largaespada LL: Explaining sex differences in dental caries prevalence: saliva, hormones, and ‘life-history’ etiologies. Am J Hum Biol 2006;18:540–555.
  12. Nakahori Y, Takenaka O, Nakagome Y: A human X-Y homologous region encodes ‘amelogenin’. Genomics 1991;9:264–269.
  13. Ranade K, Chang MS, Ting CT, Pei D, Hsiao CF, Olivier M, Pesich R, Hebert J, Chen YD, Dzau VJ, Curb D, Olshen R, Risch N, Cox DR, Botstein D: High-throughput genotyping with single nucleotide polymorphisms. Genome Res 2001;11:1262–1268.
  14. Rosen S, Hunt HR, Hoppert CA: Hereditary limitations of the infectious and transmissible nature of experimental dental caries. Arch Oral Biol 1961;5:92–97.
  15. Salido EC, Yen PH, Koprivnikar K, Yu LC, Shapiro LJ: The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes. Am J Hum Genet 1992;50:303–316.
  16. Shuler CF: Inherited risks for susceptibility to dental caries. J Dent Educ 2001;65:1038–1045.
  17. Simmer JP, Hu JCC: Dental enamel formation and its impact on clinical dentistry. J Dent Educ 2001;65:896–905.
  18. Slayton RL, Cooper ME, Marazita ML: Tuftelin, mutans streptococci, and dental caries susceptibility. J Dent Res 2005;84:711–714.
  19. Vieira AR, Marazita ML, McHenry TG: Genome-wide scan finds suggestive caries loci. J Dent Res 2008;87:435–439.
  20. Yano A, Kaneko N, Ida H, Yamaguchi T, Hanada N: Real-time PCR for quantification of Streptococcus mutans. FEMS Microbiol Lett 2002;217:23–30.
  21. Young DC, Santiago SA, Ament DK, Stark DF, Slayton RL: Association studies of acidic proline-rich salivary protein genes in caries susceptibility. J Dent Res 2002;81:A-350.
  22. Yu PL, Bixler D, Goodman PA, Azen EA, Karn RC, Rao DC: Human parotid praline-rich proteins: correlation of genetic polymorphisms to dental caries. Genet Epidemiol 1986;3:147–152.
  23. Zakhary GM, Clark RM, Bidichandani SI, Owen WL, Slayton RL, Levine M: Acidic proline-rich protein Db and caries in young children. J Dent Res 2007;86:1176–1180.

 goto top of outline Author Contacts

Alexandre R. Vieira
614 Salk Hall, Department of Oral Biology, School of Dental Medicine
University of Pittsburgh, 3501 Terrace Street
Pittsburgh, PA 15261 (USA)
Tel. +1 412 383 8972, Fax +1 412 624 3080, E-Mail arv11@dental.pitt.edu


 goto top of outline Article Information

Received: May 6, 2008
Accepted after revision: July 27, 2008
Published online: September 10, 2008
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 5, Number of References : 23


 goto top of outline Publication Details

Caries Research

Vol. 42, No. 5, Year 2008 (Cover Date: September 2008)

Journal Editor: Shellis R.P. (Bristol)
ISSN: 0008–6568 (Print), eISSN: 1421–976X (Online)

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


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes and their interaction with Streptococcus mutans levels may contribute to caries. For the present study, we used DNA samples collected from 173 unrelated children from Istanbul: 91 children with 4 or more affected tooth surfaces and 82 caries-free children. Six single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Regression analysis was used for the evaluation of individual gene effects, environmental effects and gene-environment interactions. Overrepresentation of the C allele of the amelogenin marker was seen in cases with dmft scores higher than 8 (p = 0.01) when compared to controls. Also, overrepresentation of the T allele of the ameloblastin marker was seen in cases with dmfs scores higher than 10 (p = 0.05) when compared to controls. In addition, the CT genotype of the tuftelin rs3790506 marker was overrepresented in cases with dmft scores higher than 5 (p = 0.05) and dmfs scores higher than 6 (p = 0.05) compared to controls. The best-fitting model showed that dmfs is increased when the following factors are present: (1) females and both the anterior and posterior teeth are affected simultaneously, (2) when the T allele of the tuftelin rs3790506 is involved, and (3) the C allele of the amelogenin rs17878486 is involved. Our study provides support that genes involved in enamel formation modify caries susceptibility in humans.



 goto top of outline Author Contacts

Alexandre R. Vieira
614 Salk Hall, Department of Oral Biology, School of Dental Medicine
University of Pittsburgh, 3501 Terrace Street
Pittsburgh, PA 15261 (USA)
Tel. +1 412 383 8972, Fax +1 412 624 3080, E-Mail arv11@dental.pitt.edu


 goto top of outline Article Information

Received: May 6, 2008
Accepted after revision: July 27, 2008
Published online: September 10, 2008
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 5, Number of References : 23


 goto top of outline Publication Details

Caries Research

Vol. 42, No. 5, Year 2008 (Cover Date: September 2008)

Journal Editor: Shellis R.P. (Bristol)
ISSN: 0008–6568 (Print), eISSN: 1421–976X (Online)

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


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Alvesalo L: Sex chromosomes and human growth: a dental approach. Hum Genet 1997;101:1–5.
  2. Ayad M, van Wuyckhuyse BC, Minaguchi K, Raubertas RF, Bedi GF, Billings RJ, Bowen WH, Tabak LA: The association of basic proline-rich peptides from human parotid gland secretions with caries experience. J Dent Res 2000;79:976–982.
  3. Declerck D, Leroy R, Martens L, Lesaffre E, Garcia-Zattera MJ, van den Broucke S, Debyser M, Hoppenbrouwers K: Factors associated with prevalence and severity of caries experience in preschool children. Community Dent Oral Epidemiol 2008;36:168–178.
  4. Deeley K, Letra A, Rose EK, Brandon CA, Resick JM, Marazita ML, Vieira AR: Possible association of amelogenin to high caries experience in a Guatemalan-Mayan population. Caries Res 2008;42:8–13.
  5. Hu JCC, Chun YHP, Al Hazzazzi T, Simmer JP: Enamel formation and amelogenesis imperfecta. Cell Tissues Organs 2007;186:78–85.
  6. Hunt HR, Hoppert CA, Erwin WG: Inheritance of susceptibility to caries in albino rats (Mus norvegicus). J Dent Res 1944;23:385–401.
  7. Ioannidis JPA, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG: Replication validity of genetic association studies. Nat Genet 2001;29:306–309.
  8. Klein H: The family and dental disease. IV. Dental disease (DMF) experiences in parents and offspring. J Am Dent Assoc 1946;33:735–743.

    External Resources

  9. Klein H, Palmer CE: Dental caries in brothers and sisters of immune and susceptible children. Milbank Mem Fund Q 1940;18:67–82.

    External Resources

  10. Krebsbach PH, Lee SK, Matsuli Y, Kozak CA, Yamada KM, Yamada Y: Full-length sequence, localization, and chromosomal mapping of ameloblastin: a novel tooth-specific gene. J Biol Chem 1996;271:4431–4435.
  11. Lukacs JR, Largaespada LL: Explaining sex differences in dental caries prevalence: saliva, hormones, and ‘life-history’ etiologies. Am J Hum Biol 2006;18:540–555.
  12. Nakahori Y, Takenaka O, Nakagome Y: A human X-Y homologous region encodes ‘amelogenin’. Genomics 1991;9:264–269.
  13. Ranade K, Chang MS, Ting CT, Pei D, Hsiao CF, Olivier M, Pesich R, Hebert J, Chen YD, Dzau VJ, Curb D, Olshen R, Risch N, Cox DR, Botstein D: High-throughput genotyping with single nucleotide polymorphisms. Genome Res 2001;11:1262–1268.
  14. Rosen S, Hunt HR, Hoppert CA: Hereditary limitations of the infectious and transmissible nature of experimental dental caries. Arch Oral Biol 1961;5:92–97.
  15. Salido EC, Yen PH, Koprivnikar K, Yu LC, Shapiro LJ: The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes. Am J Hum Genet 1992;50:303–316.
  16. Shuler CF: Inherited risks for susceptibility to dental caries. J Dent Educ 2001;65:1038–1045.
  17. Simmer JP, Hu JCC: Dental enamel formation and its impact on clinical dentistry. J Dent Educ 2001;65:896–905.
  18. Slayton RL, Cooper ME, Marazita ML: Tuftelin, mutans streptococci, and dental caries susceptibility. J Dent Res 2005;84:711–714.
  19. Vieira AR, Marazita ML, McHenry TG: Genome-wide scan finds suggestive caries loci. J Dent Res 2008;87:435–439.
  20. Yano A, Kaneko N, Ida H, Yamaguchi T, Hanada N: Real-time PCR for quantification of Streptococcus mutans. FEMS Microbiol Lett 2002;217:23–30.
  21. Young DC, Santiago SA, Ament DK, Stark DF, Slayton RL: Association studies of acidic proline-rich salivary protein genes in caries susceptibility. J Dent Res 2002;81:A-350.
  22. Yu PL, Bixler D, Goodman PA, Azen EA, Karn RC, Rao DC: Human parotid praline-rich proteins: correlation of genetic polymorphisms to dental caries. Genet Epidemiol 1986;3:147–152.
  23. Zakhary GM, Clark RM, Bidichandani SI, Owen WL, Slayton RL, Levine M: Acidic proline-rich protein Db and caries in young children. J Dent Res 2007;86:1176–1180.