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European Archives of Paediatric Dentistry

, Volume 14, Issue 6, pp 405–410 | Cite as

Candidate gene studies in hypodontia suggest role for FGF3

  • A. R. VieiraEmail author
  • R. N. D’Souza
  • G. Mues
  • K. Deeley
  • H. -Y. Hsin
  • E. C. Küchler
  • R. Meira
  • A. Patir
  • P. N. Tannure
  • A. Lips
  • M. C. Costa
  • J. M. Granjeiro
  • F. Seymen
  • A. Modesto
Short Communication

Abstract

Introduction

The majority of tooth agenesis cases are mild (hypodontia) and typically not associated with the gene mutations linked to oligodontia. From this, we hypothesise that most cases of tooth agenesis fit a polygenic mode of inheritance, where several genes with small effects cause a variety of varying phenotypes.

Materials and methods

In this study, we looked at 18 not typically studied genes in this condition, to ascertain their contribution to hypodontia. Our study subjects consisted of 167 patients with hypodontia and their parents from two cohorts (one from Brazil and one from Turkey). An additional 465 DNA samples (93 cases with hypodontia and 372 controls without family history for tooth agenesis or oral clefts) from Brazil were also available for this study. Ninety-three single nucleotide polymorphisms that maximally represent the linkage disequilibrium structure of the genes for the 18 genes were selected and genotyped using Taqman chemistry. Chi square was used to test if genotype distributions were in Hardy–Weinberg equilibrium, and 24 markers that were in Hardy–Weinberg equilibrium and had allele frequencies higher than 5 % in a panel of 50 CEPH samples were further tested. Association between hypodontia and genetic variants was tested with the transmission disequilibrium test within the programme Family-Based Association Test (FBAT) and by using Chi square and Fisher’s exact tests. Alpha at a level of 0.05 was used to report results.

Results

Results suggest possible associations between several genes and hypodontia in the three populations. In the Turkish cohort (n = 51 parent–affected child trios) the most significant results were as follows: FGF3 rs1893047, p = 0.08; GLI3 rs929387, p = 0.03; GLI3 haplotype rs929387-rs846266, p = 0.002; and PAX9 rs2073242, p = 0.03. In the Brazilian cohort (n = 116 parent–affected child trios), the results were as follows: DLX1 rs788173, p = 0.07; FGF3 rs12574452, p = 0.03; GLI2 rs1992901, p = 0.03; and PITX2 rs2595110, p = 0.01. The second Brazilian cohort also suggested that FGF3 (rs12574452, p = 0.01) is associated with hypodontia and added EDAR (rs17269487, p = 0.04), LHX6 (rs989798, p = 0.02), and MSX1 (rs12532, p = 0.003).

Conclusion

Our results suggest that several genes are potentially associated with hypodontia and their individual contributions may be modest. Hence, these cases may not be explained by inactivating mutations such as many oligodontia cases segregating in a Mendelian fashion but rather are influenced by one or more susceptibility alleles in multiple small effect genes.

Keywords

Tooth abnormalities Odontogenesis MSX1 PAX9 PITX2 

Notes

Acknowledgments

This work was supported by the United States National Institutes of Health Grant R01 DE019471 (R.N.D’S) and its administrative supplement (to R.N.D’S and A.R.V).

Conflict of interest

None of the authors have any conflict of interest to declare.

Author contributions

Data analysis: K.D., H-Y.H, E.C.K., A.R.V

Study design: R.N.D'S., G.M., E.C.K., R.M., A.P., M.C.C., J.M.G., F.S., A.M., A.R.V.

Obtaining funding: R.N.D'S., M.C.C., J.M.G., F.S., A.R.V., A.M.

Manuscript writing: A.R.V.

Data collection: E.C.K., R.M., A.P., P.N.T., A.L.

DNA Manipulation/Genotyping: K.D., H-Y.H, E.C.K., A.P., A.L.

Revising and reviewing paper: R.N.D'S., G.M., K.D., H-Y.H, E.C.K., R.M., A.P., P.N.T., A.L., M.C.C., J.M.G., F.S., A.M., A.R.V.

Supplementary material

40368_2013_10_MOESM1_ESM.docx (55 kb)
Supplementary material 1 (DOCX 54 kb)
40368_2013_10_MOESM2_ESM.docx (44 kb)
Supplementary material 2 (DOCX 43 kb)

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Copyright information

© European Academy of Paediatric Dentistry 2013

Authors and Affiliations

  • A. R. Vieira
    • 1
    • 2
    Email author
  • R. N. D’Souza
    • 3
  • G. Mues
    • 3
  • K. Deeley
    • 1
  • H. -Y. Hsin
    • 1
  • E. C. Küchler
    • 1
  • R. Meira
    • 4
  • A. Patir
    • 6
  • P. N. Tannure
    • 4
    • 5
  • A. Lips
    • 4
  • M. C. Costa
    • 4
  • J. M. Granjeiro
    • 7
  • F. Seymen
    • 8
  • A. Modesto
    • 1
    • 2
  1. 1.Department of Oral BiologySchool of Dental Medicine, University of PittsburghPittsburghUSA
  2. 2.Department of Pediatric DentistrySchool of Dental Medicine, University of PittsburghPittsburghUSA
  3. 3.Department of Biomedical SciencesTexas A&M Health Science Center Baylor College of DentistryDallasUSA
  4. 4.Department of Pediatric Dentistry and OrthodonticsFederal University of Rio de JaneiroRio de JaneiroBrazil
  5. 5.Discipline of Pediatric DentistryVeiga de Almeida UniversityRio de JaneiroBrazil
  6. 6.Department of PedodonticsMedipol Istanbul UniversityIstanbulTurkey
  7. 7.Biology Institute, Clinical Research Unit, Fluminense Federal University, Niterói, and INMETRORio de JaneiroBrazil
  8. 8.Department of PedodonticsIstanbul UniversityIstanbulTurkey

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