Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Enamel and enameloid, the highly mineralized tooth-covering tissues in living vertebrates, are different in their matrix composition. Enamel, a unique product of ameloblasts, principally contains enamel matrix proteins (EMPs), while enameloid possesses collagen fibrils and probably receives contributions from both odontoblasts and ameloblasts. Here we focused on type I collagen (COL1A1) and amelogenin (AMEL) gene expression during enameloid and enamel formation throughout ontogeny in the caudate amphibian, Pleurodeles waltl. In this model, pre-metamorphic teeth possess enameloid and enamel, while post-metamorphic teeth possess enamel only. In first-generation teeth, qPCR and in situ hybridization (ISH) on sections revealed that ameloblasts weakly expressed AMEL during late-stage enameloid formation, while expression strongly increased during enamel deposition. Using ISH, we identified COL1A1 transcripts in ameloblasts and odontoblasts during enameloid formation. COL1A1 expression in ameloblasts gradually decreased and was no longer detected after metamorphosis. The transition from enameloid-rich to enamel-rich teeth could be related to a switch in ameloblast activity from COL1A1 to AMEL synthesis. P. waltl therefore appears to be an appropriate animal model for the study of the processes involved during enameloid-to-enamel transition, especially because similar events probably occurred in various lineages during vertebrate evolution.
ISSN: 0022-0345

hal-01545475
https://hal.archives-ouvertes.fr/hal-01545475
DOI : 10.1177/0022034514526236

Résumé : The slides were taken on collecting trips sponsored by the William L. Bryant Foundation, where books, music and art indigenous to the regions were gathered. The are organized by geographical location.
A woman wearing a white hat stands in front of steps leading to a house. The image also shows two enamel and one metal wash basins filled with clothes. On the house's verandah are tables and chairs. Inhabitants of Moore Town, Portland, Jamaica are descendants of Maroons, escaped slaves who were able to maintain some aspects of their African cultures. Slide labeled Jam. Moore Town.
Jamaica -- Caribbean region -- Moore Town, Portland

Droits : All rights to images are held by the respective holding institution. This image is posted publicly for non-profit educational uses, excluding printed publication. For permission to reproduce images and/or for copyright information contact Special Collections & University Archives, University of Central Florida Libraries, Orlando, FL 32816 phone (407) 823-2576, email: speccoll@mail.ucf.edu
CFM1972_01a
http://ufdc.ufl.edu/AA00031032/00001

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Ameloblastin (AMBN) is a phosphorylated, proline/glutamine-rich protein secreted during enamel formation. Previous studies have revealed that this enamel matrix protein was present early in vertebrate evolution and certainly plays important roles during enamel formation although its precise functions remain unclear. We performed evolutionary analyses of AMBN in order to (i) identify residues and motifs important for the protein function, (ii) predict mutations responsible for genetic diseases, and (iii) understand its molecular evolution in mammals. Results: In silico searches retrieved 56 complete sequences in public databases that were aligned and analyzed computationally. We showed that AMBN is globally evolving under moderate purifying selection in mammals and contains a strong phylogenetic signal. In addition, our analyses revealed codons evolving under significant positive selection. Evidence for positive selection acting on AMBN was observed in catarrhine primates and the aye-aye. We also found that (i) an additional translation initiation site was recruited in the ancestral placental AMBN, (ii) a short exon was duplicated several times in various species including catarrhine primates, and (iii) several polyadenylation sites are present. Conclusions: AMBN possesses many positions, which have been subjected to strong selective pressure for 200 million years. These positions correspond to several cleavage sites and hydroxylated, O-glycosylated, and phosphorylated residues. We predict that these conserved positions would be potentially responsible for enamel disorder if substituted. Some motifs that were previously identified as potentially important functionally were confirmed, and we found two, highly conserved, new motifs, the function of which should be tested in the near future. This study illustrates the power of evolutionary analyses for characterizing the functional constraints acting on proteins with yet uncharacterized structure.
ISSN: 1471-2148

Droits : http://creativecommons.org/licenses/by/
hal-01212816
http://hal.upmc.fr/hal-01212816
http://hal.upmc.fr/hal-01212816/document
http://hal.upmc.fr/hal-01212816/file/s12862-015-0431-0.pdf
DOI : 10.1186/s12862-015-0431-0

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new causal Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop codon (p.N120fz*2). We characterized the enamel structure of the latter case using scanning electron microscopy analysis and microanalysis (Energy-dispersive X-ray Spectroscopy, EDX) and confirmed the hypomaturation-type amelogenesis imperfecta as identified in the clinical diagnosis. The mineralized content was slightly decreased, with magnesium substituting for calcium in the crystal structure. The anomalies affected enamel with minimal inter-rod enamel present and apatite crystals perpendicular to the enamel prisms, suggesting a possible new role for MMP20 in enamel formation.
ISSN: 0022-0345

hal-01545484
https://hal.archives-ouvertes.fr/hal-01545484
DOI : 10.1177/0022034513488393

Éditeur(s) : HAL CCSD
Résumé : Enamel formation requires the involvement of secretory calcium-binding phosphoproteins. Three of them, amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM), have been extensively studied in mammals. More recently, a fourth protein belonging to the same family has been identified: amelotin (AMTN). AMTN has only been studied in rodents and its role during amelogenesis remains unclear.The aim of this thesis is to extend the knowledge on AMTN by studying its evolution in amniotes and its expression in the lizard Anolis carolinensis.AMTN sequences from many amniote species have been extracted from databases or obtained by PCR, and analyzed. Those analyses allowed us to reveal differences in the gene structure and to highlight residues that were conserved during mammalian or amniote evolution. These conserved amino acids are essential to the structure and/or function of the protein.The expression of AMTN and of AMEL, AMBN and ENAM has been studied by in situ hybridization on lizard jaw sections. Comparison of the expression pattern of these genes during amelogenesis in the lizard with that described in rodents points to similarities (AMEL, AMBN and ENAM) but also to important differences, especially in the spatio-temporal expression of AMTN. In order to better understand AMTN evolution in tetrapods, I studied its expression in an amphibian (Pleurodeles waltl) and a marsupial (Monodelphis domestica).Taken together, these results suggest a link between the evolution of AMTN gene structure (loss of exons and of functional domains in mammals) and its expression (early in non-mammals versus late in mammals) with the emergence of prismatic structure of enamel in early mammals.
La formation de l'émail dentaire met en jeu des phosphoprotéines sécrétées liant le calcium. Parmi celles-ci figurent amélogénine (AMEL), améloblastine (AMBN) et énaméline (ENAM), qui ont fait l'objet de nombreuses études chez les mammifères. Plus récemment, une quatrième protéine de la même famille a été découverte, l'amélotine (AMTN). Elle n'a été étudiée que chez les rongeurs et son rôle au cours de l'amélogenèse reste mal défini. L'objectif de cette thèse est d'élargir les connaissances sur AMTN en étudiant son évolution chez les amniotes et son expression au cours de l'amélogenèse chez le lézard Anolis carolinensis. Les séquences d'AMTN d'un grand nombre d'amniotes ont été extraites des bases de données ou obtenues par PCR, et analysées. Ces analyses ont mis en évidence différentes structures géniques et des acides aminés très conservés au cours de l'évolution. Cette conservation indique qu'ils sont essentiels à la structure ou à la fonction de la protéine. L'expression d'AMTN ainsi que celle d'AMEL, AMBN et ENAM ont été étudiées par hybridation in situ sur des coupes de mâchoires de lézard. La comparaison des patrons d'expression chez le lézard avec ceux décrits chez la souris a révélé des différences dans l'expression spatio-temporelle d'AMTN. De ce fait, afin de mieux comprendre l'évolution de ce gène, son expression a été étudiée chez un amphibien (Pleurodeles waltl) et un marsupial (Monodelphis domestica).Ces travaux suggère un lien entre l'évolution de la structure génique d'AMTN (perte d'exons et de domaines fonctionnels) et de son expression (précoce versus tardive) avec l'émergence de la structure prismatique de l'émail chez les mammifères.
https://tel.archives-ouvertes.fr/tel-01154518

NNT : 2015PA066066
tel-01154518
https://tel.archives-ouvertes.fr/tel-01154518
https://tel.archives-ouvertes.fr/tel-01154518/document
https://tel.archives-ouvertes.fr/tel-01154518/file/2015PA066066.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Well studied in mammals, amelogenesis is less known at the molecular level in reptiles and amphibians. In the course of extensive studies of enamel matrix protein (EMP) evolution in tetrapods, we look for correlation between changes in protein sequences and temporospatial protein gene expression during amelogenesis, using an evo-devo approach. Our target is the major EMP, amelogenin (AMEL) that plays a crucial role in enamel structure. We focused here our attention to an amphibian, the salamander Pleurodeles waltl. RNAs were extracted from the lower jaws of a juvenile P. waltl and the complete AMEL sequence was obtained using PCR and RACE PCR. The alignment of P. waltl AMEL with other tetrapodan (frogs, reptiles and mammals) sequences revealed residue conservation in the N- and C-terminal regions, and a highly variable central region. Using sense and anti-sense probes synthetized from the P. waltl AMEL sequence, we performed in situ hybridization on sections during amelogenesis in larvae, juveniles, and adults. We demonstrated that (i) AMEL expression was always found to be restricted to ameloblasts, (ii) the expression pattern was conserved through ontogeny, even in larvae where enameloid is present in addition to enamel, and (iii) the processes are similar to those described in lizards and mammals. These findings indicate that high variations in the central region of AMEL have not modified its temporospatial expression during amelogenesis for 360 million years of tetrapod evolution. J. Exp. Zool. (Mol. Dev. Evol.) 320B:200209, 2013.
ISSN: 1552-5007

hal-01545483
https://hal.archives-ouvertes.fr/hal-01545483
DOI : 10.1002/jez.b.22494

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Molecular evolutionary analysis is an efficient method to predict and/or validate amino acid substitutions that could lead to a genetic disease and to highlight residues and motifs that could play an important role in the protein structure and/or function. We have applied such analysis to amelotin (AMTN), a recently identified enamel protein in the rat, mouse, and humans. An in silico search for AMTN provided 42 new mammalian sequences that were added to the 3 published sequences with which we performed the analysis using a dataset representative of all lineages (circa 220 million years of evolution), including 2 enamel-less species, sloth and armadillo. During evolution, of the 209 residues of human AMTN, 17 were unchanged and 34 had conserved their chemical properties. Substituting these important residues could lead to amelogenesis imperfecta (AI). Also, AMTN possesses a well-conserved signal peptide, 2 conserved motifs whose function is certainly important but unknown, and a putative phosphorylation site (SXE). In addition, the sequences of the 2 enamel-less species display mutations revealing that AMTN underwent pseudogenization, which suggests that AMTN is an enamel-specific protein.
ISSN: 0022-0345

hal-01545488
https://hal.archives-ouvertes.fr/hal-01545488
DOI : 10.1177/0022034512460551

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background : In a recent study, we have demonstrated that amelotin (AMTN) gene structure and its expression during amelogenesis have changed during tetrapod evolution. Indeed, this gene is expressed throughout enamel matrix deposition and maturation in non-mammalian tetrapods, while in mammals its expression is restricted to the transition and maturation stages of amelogenesis. Previous studies of amelogenin (AMEL) gene expression in a lizard and a salamander have shown similar expression pattern to that in mammals, but to our knowledge there are no data regarding ameloblastin (AMBN) and enamelin (ENAM) expression in non-mammalian tetrapods. The present study aims to look at, and compare, the structure and expression of four enamel matrix protein genes, AMEL, AMBN, ENAM and AMTN during amelogenesis in the lizard Anolis carolinensis.Results : We provide the full-length cDNA sequence of A. carolinensis AMEL and AMBN, and show for the first time the expression of ENAM and AMBN in a non-mammalian species. During amelogenesis in A. carolinensis, AMEL, AMBN and ENAM expression in ameloblasts is similar to that described in mammals. It is noteworthy that AMEL and AMBN expression is also found in odontoblasts. Conclusions : Our findings indicate that AMTN is the only enamel matrix protein gene that is differentially expressed in ameloblasts between mammals and sauropsids. Changes in AMTN structure and expression could be the key to explain the structural differences between mammalian and reptilian enamel, i.e. prismatic versus non-prismatic.
ISSN: 2041-9139

Droits : http://creativecommons.org/licenses/by/
hal-01206550
http://hal.upmc.fr/hal-01206550
http://hal.upmc.fr/hal-01206550/document
http://hal.upmc.fr/hal-01206550/file/Gasse_2015_Comparative.pdf
DOI : 10.1186/s13227-015-0024-4

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Amelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein (SCPP) family, which originated in early vertebrates. In rodents, AMTN is expressed during the maturation stage of amelogenesis only. This expression pattern strongly differs from the spatiotemporal expression of other ameloblast-secreted SCPPs, such as the enamel matrix proteins (EMPs). Furthermore, AMTN was characterized in rodents only. In this study, we applied various approaches, including in silico screening of databases, PCRs and transcriptome sequencing to characterize AMTN sequences in sauropsids and amphibians, and compared them to available mammalian and coelacanth sequences. Results: We showed that (i) AMTN is tooth (enamel) specific and underwent pseudogenization in toothless turtles and birds, and (ii) the AMTN structure changed during tetrapod evolution. To infer AMTN function, we studied spatiotemporal expression of AMTN during amelogenesis in a salamander and a lizard, and compared the results with available expression data from mouse. We found that AMTN is expressed throughout amelogenesis in non-mammalian tetrapods, in contrast to its expression limited to enamel maturation in rodents. Conclusions: Taken together our findings suggest that AMTN was primarily an EMP. Its functions were conserved in amphibians and sauropsids while a change occurred early in the mammalian lineage, modifying its expression pattern during amelogenesis and its gene structure. These changes likely led to a partial loss of AMTN function and could have a link with the emergence of prismatic enamel in mammals.
ISSN: 1471-2148

Droits : http://creativecommons.org/licenses/by/
hal-01212821
http://hal.upmc.fr/hal-01212821
http://hal.upmc.fr/hal-01212821/document
http://hal.upmc.fr/hal-01212821/file/s12862-015-0329-x.pdf
DOI : 10.1186/s12862-015-0329-x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Dental and postcranial remains (an atlas, carpus and metacarpus elements, and a part of the pelvic girdle) of an embrithopod mammal are described from Bir Om Ali, Tunisia, a new late Eocene locality. The enamel microstructure of a tooth fragment found in association shows 'arsinoitheriid radial enamel', an enamel condition which is characteristic of Arsinoitherium (Arsinoitheriidae, Embrithopoda). Although the postcranial elements slightly differ in size and morphology from those of Arsinoitherium zitteli (late Eocene to early Oligocene), we tentatively refer this new Eocene Tunisian material to that genus. These fossils represent the first known embrithopod from the Eocene of Tunisia.
ISSN: 0899-5362

hal-00903435
https://hal.archives-ouvertes.fr/hal-00903435
DOI : 10.1016/j.jafrearsci.2013.07.010

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Amelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein family, which also includes the enamel matrix proteins amelogenin, ameloblastin and enamelin. Although AMTN is supposed to play an important role in enamel formation, data were long limited to the rodents, in which it is expressed during the maturation stage. Recent comparative studies in sauropsids and amphibians revealed that (i) AMTN was expressed earlier, i.e. as soon as ameloblasts are depositing the enamel matrix, and (ii) AMTN structure was different, a change which mostly resulted from an intraexonic splicing in the large exon 8 of an ancestral mammal. The present study was performed to know whether the differences in AMTN structure and expression in rodents compared to non-mammalian tetrapods dated back to an early ancestral mammal or were acquired later in mammalian evolution. We sequenced, assembled and screened the jaw transcriptome of a neonate opossum Monodelphis domestica, a marsupial. We found two AMTN transcripts. Variant 1, representing 70.8% of AMTN transcripts, displayed the structure known in rodents, whereas variant 2 (29.2%) exhibited the nonmammalian tetrapod structure. Then, we studied AMTN expression during amelogenesis in a neonate specimen. We obtained similar data as those reported in rodents. These findings indicate that more than 180 million years ago, before the divergence of marsupials and placentals, changes occurred in AMTN function and structure. The spatiotemporal expression was delayed to the maturation stage of amelogenesis and the intraexonic splicing gave rise to isoform 1, encoded by variant 1 and lacking the RGD motif. The ancestral isoform 2, housing the RGD, was initially conserved, as demonstrated here in a marsupial, then secondarily lost in the placental lineages. These findings bring new elements towards our understanding of the non-prismatic to prismatic enamel transition that occurred at the onset of mammals.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552/document
https://hal.archives-ouvertes.fr/hal-01233552/file/journal.pone.0133314.pdf
DOI : 10.1371/journal.pone.0133314

Éditeur(s) : HAL CCSD Elsevier Elsevier Masson
Résumé : Thalattosuchia was a diverse clade of marine crocodylomorphs known from the Early Jurassic to the Early Cretaceous. Recent studies have hypothesized that their extinction was two-phased: (1) habitat loss near/at the Jurassic-Cretaceous boundary heavily reduced their morphofunctional diversity, particularly in Europe, while (2) climate change and a shift in marine fauna during the Early Cretaceous (either at the Valanginian-Hauterivian boundary or during the early Hauterivian) finished off the already stressed clade. Unfortunately, the Cretaceous fossil record of thalattosuchians is poor, with only one putative “teleosaurid” specimen and approximately ten metriorhynchid specimens. Here we re-describe the youngest known teleosaurid from the Cretaceous (Valanginian of south-eastern France). Originally considered to be a teleosaurid (possibly Steneosaurus), we demonstrate that it belongs to Metriorhynchidae, and a newly discovered subclade, Plesiosuchina. It differs from Plesiosuchus in the pattern of tooth enamel ornamentation and the variation in dentary alveoli size. Referring this specimen to Metriorhynchidae means there are no definitive Cretaceous teleosaurid specimens. Furthermore, it suggests that both durophagous and piscivorous teleosaurids became extinct at the end of the Jurassic. Interestingly, this is the fourth metriorhynchid lineage known to cross the Jurassic-Cretaceous boundary. As such, it would appear that the two thalattosuchian families responded very differently to the lowering sea levels at the end of the Jurassic: teleosaurids possibly became extinct, while metriorhynchids were seemingly unaffected.
ISSN: 0753-3969

hal-01122803
https://hal.archives-ouvertes.fr/hal-01122803
DOI : 10.1016/j.annpal.2014.01.002

Éditeur(s) : HAL CCSD American Academy of Pediatrics
Résumé : International audience
Vitamin D is an essential hormone for calcium gut absorption. It is also involved in child growth, cancer prevention, immune system responses, and tooth formation. Due to inadequate vitamin D intake and/or decreased sunlight exposure, vitamin D deficiency has resurfaced in developed countries despite known inexpensive and effective preventive methods. Vitamin D deficiency is a common cause of rickets, a condition that affects bone development in children and that can have serious dental complications. Deficiency during pregnancy can cause enamel hypoplasia of primary teeth. Enamel regeneration is currently impossible; hypoplasia is therefore irreversible, and once affected, teeth are prone to fast caries development. Deficiency during early childhood can affect permanent teeth and ensuing caries can sometimes lead to tooth loss at a young age. Oral manifestations of rickets should be diagnosed early by both physicians and dentists to prevent severe dental complications. This case study presents 2 young girls with rickets in early childhood who suffered from subsequent serious tooth decay.
ISSN: 0031-4005

hal-01545477
https://hal.archives-ouvertes.fr/hal-01545477
DOI : 10.1542/peds.2013-0733

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Genetic approaches have shown that several genes could modify caries susceptibility; AmelogeninX (AMELX) has been repeatedly designated. Here, we hypothesized that AMELX mutations resulting in discrete changes of enamel microstructure may be found in children with a severe caries phenotype. In parallel, possible AMELX mutations that could explain resistance to caries may be found in caries-free patients. In this study, coding exons of AMELX and exon-intron boundaries were sequenced in 399 individuals with extensive caries (250) or caries-free (149) individuals from nine French hospital groups. No mutation responsible for a direct change of amelogenin function was identified. Seven single-nucleotide polymorphisms (SNPs) were found, 3 presenting a high allele frequency, and 1 being detected for the first time. Three SNPs were located in coding regions, 2 of them being non-synonymous. Both evolutionary and statistical analyses showed that none of these SNPs was associated with caries susceptibility, suggesting that AMELX is not a gene candidate in our studied population.
ISSN: 0022-0345

hal-01545481
https://hal.archives-ouvertes.fr/hal-01545481
DOI : 10.1177/0022034513482941

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Amelogenin gene organization varies from 6 exons (1,2,3,5,6,7) in amphibians and sauropsids to 10 in rodents. The additional exons are exons 4, 8, 9, and ``4b'', the latter being as yet unidentified in AMELX transcripts. To learn more about the evolutionary origin of these exons, we used an in silico approach to find them in 39 tetrapod genomes. AMEL organization with 6 exons was the ancestral condition. Exon 4 was created in an ancestral therian (marsupials + placentals), then exon 9 in an ancestral placental, and finally exons ``4b'' and 8 in rodents, after divergence of the squirrel lineage. These exons were either inactivated in some lineages or remained functional: Exon 4 is functional from artiodactyls onward; exon 9 is known, to date, only in rodents, but could be coding in various mammals; and exon ``4b'' was probably coding in some rodents. We performed PCR of cDNA isolated from mouse and human tooth buds to identify the presence of these transcripts. A sequence analogous to exon ``4b'', and to exon 9, could not be amplified from the respective tooth cDNA, indicating that even though sequences similar to these exons are present, they are not transcribed in these species.
ISSN: 0022-0345

hal-01545487
https://hal.archives-ouvertes.fr/hal-01545487
DOI : 10.1177/0022034511423399

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Tuftelin (TUFT1) is an acidic, phosphorylated glycoprotein, initially discovered in developing enamel matrix. TUFT1 is expressed in many mineralized and non-mineralized tissues. We performed an evolutionary analysis of 82 mammalian TUFT1 sequences to identify residues and motifs that were conserved during 220 million years (Ma) of evolution. We showed that 168 residues (out of the 390 residues composing the human TUFT1 sequence) are under purifying selection. Our analyses identified several, new, putatively functional domains and confirmed previously described functional domains, such as the TIP39 interaction domain, which correlates with nuclear localization of the TUFT1 protein, that was demonstrated in several tissues. We also identified several sites under positive selection, which could indicate evolutionary changes possibly related to the functional diversification of TUFT1 during evolution in some lineages. We discovered that TUFT1 and MYZAP (myocardial zonula adherens protein) share a common ancestor that was duplicated circa 500 million years ago. Taken together, these findings expand our knowledge of TUFT1 evolution and provide new information that will be useful for further investigation of TUFT1 functions.
ISSN: 0022-2844

hal-01516886
http://hal.upmc.fr/hal-01516886
http://hal.upmc.fr/hal-01516886/document
http://hal.upmc.fr/hal-01516886/file/Delgado_2017_Evolutionary.pdf
DOI : 10.1007/s00239-017-9789-5

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
In the literature, the enamelin gene ENAM has been repeatedly designated as a possible candidate for caries susceptibility. Here, we checked whether ENAM variants could increase caries susceptibility. To this aim, we sequenced coding exons and exon-intron boundaries of ENAM in 250 children with a severe caries phenotype and in 149 caries-free patients from 9 French hospital groups. In total, 23 single-nucleotide polymorphisms (SNPs) were found, but none appeared to be responsible for a direct change of ENAM function. Six SNPs had a high minor allele frequency (MAF) and 6 others were identified for the first time. Statistical and evolutionary analyses showed that none of these SNPs was associated with caries susceptibility or caries protection when studied separately and challenged with environmental factors. However, haplotype interaction analysis showed that the presence, in a same variant, of 2 exonic SNPs (rs7671281 and rs3796704; MAF 0.12 and 0.10, respectively), both changing an amino acid in the protein region encoded by exon 10 (p.I648T and p.R763Q, respectively), increased caries susceptibility 2.66-fold independent of the environmental risk factors. These findings support ENAM as a gene candidate for caries susceptibility in the studied population.
ISSN: 0022-0345

hal-01545476
https://hal.archives-ouvertes.fr/hal-01545476
DOI : 10.1177/0022034514522060