Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta
Dentinogenesis imperfecta Type II (DGI-II) is a condition inherited as an autosomal dominant trait and characterized by abnormal dentine structure affecting both the primary and secondary dentitions. The genetic etiology of the disease still remains unclear, suggesting a genetically heterogeneous ba...
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irk-123456789-1265922017-11-28T03:02:40Z Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta Ulucan, K. Akyüz, S. Özbay, G. Pekiner, F.N. A. İlter Güney Dentinogenesis imperfecta Type II (DGI-II) is a condition inherited as an autosomal dominant trait and characterized by abnormal dentine structure affecting both the primary and secondary dentitions. The genetic etiology of the disease still remains unclear, suggesting a genetically heterogeneous background. The aim of this study is to manifest briefly DGI-II and to investigate the association between BsmI, TaqI and FokI polymorphisms of Vitamin D receptor (VDR) gene and dentinogenesis imperfecta type II in a Turkish family by PCR-RFLP methodology. The affected mother and her two affected daughters were bb for BsmI polymorphism, whereas her unaffected son and her husband were Bb for the same polymorphism. One of the affected children was tt, the rest of the family were Tt for TaqI polymorphism, and all of the enrolled subjects were FF for FokI polymorphism. As a conclusion, BsmI polymorphism bb seems to be associated with (DGI-II), but should be examined in larger numbers in order to be considered as a risk factor. Неполный дентиногенез II типа (DGI-II) – состояние, которое наследуется как аутосомный доми-нантный признак и характеризуется как аномальная структура дентина, которая затрагивает первичный и вторичный рост зубов. Генетическая этиология заболевания все еще остается неизученной, но предполагается, что имеет генетически гетерогенную основу. Целью работы было с помощью PCR-RFLP оценить DGI-II и изучить связь между полиморфизмом BsmI, TaqI и FokI гена VDR и неполным дентиногенезом II типа в одной из турецких семей. Затронутые болезнью мать и две дочери были рецессивными гомозиготами bb в отношении полиморфизма BsmI, в то время как здоровый сын и муж были гетерозиготами Bb. По TaqI полиморфизму одна из больных дочерей была tt, а остальные члены семьи – Tt. Все перечисленные члены семьи были FF по полиморфизму FokI. Очевидно, полиморфизм bb BsmI связан с DGI-II, однако необходимо исследование большей выборки, чтобы считать его фактором риска. 2013 Article Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta / K. Ulucan, S. Akyüz, G. Özbay, F.N. Pekiner, A. İlter Güney // Цитология и генетика. — 2013. — Т. 47, № 5. — С. 28-32. — Бібліогр.: 25 назв. — англ. 0564-3783 DOI: 10.3103/S0095452713050101 http://dspace.nbuv.gov.ua/handle/123456789/126592 en Цитология и генетика Інститут клітинної біології та генетичної інженерії НАН України |
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Dentinogenesis imperfecta Type II (DGI-II) is a condition inherited as an autosomal dominant trait and characterized by abnormal dentine structure affecting both the primary and secondary dentitions. The genetic etiology of the disease still remains unclear, suggesting a genetically heterogeneous background. The aim of this study is to manifest briefly DGI-II and to investigate the association between BsmI, TaqI and FokI polymorphisms of Vitamin D receptor (VDR) gene and dentinogenesis imperfecta type II in a Turkish family by PCR-RFLP methodology. The affected mother and her two affected daughters were bb for BsmI polymorphism, whereas her unaffected son and her husband were Bb for the same polymorphism. One of the affected children was tt, the rest of the family were Tt for TaqI polymorphism, and all of the enrolled subjects were FF for FokI polymorphism. As a conclusion, BsmI polymorphism bb seems to be associated with (DGI-II), but should be examined in larger numbers in order to be considered as a risk factor. |
| format |
Article |
| author |
Ulucan, K. Akyüz, S. Özbay, G. Pekiner, F.N. A. İlter Güney |
| spellingShingle |
Ulucan, K. Akyüz, S. Özbay, G. Pekiner, F.N. A. İlter Güney Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta Цитология и генетика |
| author_facet |
Ulucan, K. Akyüz, S. Özbay, G. Pekiner, F.N. A. İlter Güney |
| author_sort |
Ulucan, K. |
| title |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta |
| title_short |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta |
| title_full |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta |
| title_fullStr |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta |
| title_full_unstemmed |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta |
| title_sort |
evaluation of vitamin d receptor (vdr) gene polymorphisms (foki, taqi and apai) in a family with dentinogenesis imperfecta |
| publisher |
Інститут клітинної біології та генетичної інженерії НАН України |
| publishDate |
2013 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/126592 |
| citation_txt |
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta / K. Ulucan, S. Akyüz, G. Özbay, F.N. Pekiner, A. İlter Güney // Цитология и генетика. — 2013. — Т. 47, № 5. — С. 28-32. — Бібліогр.: 25 назв. — англ. |
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Цитология и генетика |
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| fulltext |
28 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. Ò. 47. ¹ 5
Dentinogenesis imperfecta Type II (DGI-II) is a condition
inherited as an autosomal dominant trait and characterized
by abnormal dentine structure affecting both the primary
and secondary dentitions. The genetic etiology of the
disease still remains unclear, suggesting a genetically
heterogeneous background. The aim of this study is to
manifest briefly DGI-II and to investigate the association
between BsmI, TaqI and FokI polymorphisms of Vitamin
D receptor (VDR) gene and dentinogenesis imperfecta type
II in a Turkish family by PCR-RFLP methodology. The
affected mother and her two affected daughters were bb
for BsmI polymorphism, whereas her unaffected son and
her husband were Bb for the same polymorphism. One of
the affected children was tt, the rest of the family were Tt
for TaqI polymorphism, and all of the enrolled subjects
were FF for FokI polymorphism. As a conclusion, BsmI
polymorphism bb seems to be associated with (DGI-II) ,
but should be examined in larger numbers in order to be
considered as a risk factor.
Key words: dentinogenesis imperfecta, vitamin D receptor
gene, polymorphism.
Introduction. Dentin matrix is secreted by odon-
toblasts in the development of dental tooth germs
following a series of interactions between the oral
ectoderm and underlying neural-crest-derived ecto-
mesenchyme. The dentin matrix mineralizes fol-
lowing its secretion. Subsequently, odontoblasts mig-
rate toward the pulp; leaving odontoblast processes
within the matrix [1]. Resulting dentin has uni-
que structural and mechanical properties. The mi-
neral content and microhardness of dentin are
between those of enamel and bone, allowing it to
support enamel and to endure masticatory forces.
Odontoblast processes organize the structure of the
mineralized matrix into peritubular and intertubu-
lar regions and project cellular capabilities, such as
the reception of sensory information and responses
against noxious stimuli through the entire thickness
of dentin and to the dentin and to the dentino-
enamel junction [2].
While hereditary conditions affecting dentin
have long been observed, the ‘hereditary opalescent
dentin’ was adopted to describe conditions of
diseases consisting of only dental phenotypes [3].
Likewise, the term ‘dentinogenesis imperfecta’ was
introduced to describe the common dental phe-
notypes of osteogenesis imperfecta and hereditary
opalescent dentin [4].
According to the classification proposed by
Shields et al. [5], dentinogenesis imperfecta (DGI)
was originally classified into three subgroups–types
I, II and III (DGI-I-III) – based on various patterns
of dentin defects. Dentinogenesis imperfecta type I
(DGI-I) (MIM 125490) was further classified into
a syndromic form with osteogenesis imperfecta
(OI), which was further classified into collagenous
and noncollagenous forms. The classification was
based on compartmentalizing the phenotypic va-
riation into groups. Recently, Kim and Simmer
[6] proposed revising the Shields classification of
DGI. They pointed out that dentin dysplasia type
II (DD-II), DGI-II (MIM 125490), and DGI-III
(MIM 125500) represented allelic diseases with
dentin sialophosphoprotein (DSPP) mutations that
highlighted differences in clinical severity. Denti-
nogenesis imperfecta type II is an autosomal-do-
minant dentin disorder referred to as opalescent
dentin with almost complete penetrance. The
estimated prevalence of DGI-II is between 1:6.000
and 1:8.000 in the USA [7, 8]. Both deciduous and
permanent dentitions are affected in DGI-II and
exhibit short roots, bulbous-shaped crowns caused
by cervical constrictions, and the root canals and
pulp chambers are usually obliterated [9]. Histo-
logical analysis shows dysplastic appearing dentin
with irregular dentin tubules and areas completely
lacking dentin tubules.
Recent studies have shown that defects in the
dentin sialophosphoprotein (DSPP) gene cause
DGI-II [9–13], DGI-III [14], and DD-II [15].
To date, despite the existence of other candidate
genes for hereditary dentin defects [16], no disease-
K. ULUCAN 1, S. AKYÜZ 2, G. ÖZBAY 2, F.N. PEKINER 2, A. LTER GÜNEY 3
1 Uskudar University, Faculty of Engineering and Natural Sciences, Istanbul, Turkey
2 Marmara University, Faculty of Dentistry, Istanbul, Turkey
3 Marmara University, Faculty of Medicine, Istanbul, Turkey
E-mail: korkutulucan@hotmail.com
EVALUATION OF VITAMIN D RECEPTOR (VDR) GENE POLYMORPHISMS
(FokI, TaqI AND ApaI) IN A FAMILY WITH DENTINOGENESIS IMPERFECTA
© K. ULUCAN, S. AKYÜZ, G. ÖZBAY, F.N. PEKINER,
A. LTER GÜNEY, 2013
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI)
ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. Ò. 47. ¹ 5 29
causing mutations outside of the DSPP gene have
been identified [17].
Tooth formation and dentin development re-
quires genetic and environmental factors in
which both of the factors play crucial roles. One
of the environmental factors that effect dentin
mineralization is Vitamin D [18] which maintains
calcium and phosphorus level. Vitamin D is a fat-
soluble vitamin and regulates variety of biological
processes like bone and dentin development via
its’ ligand dependent receptor, vitamin D receptor
(VDR) [19]. VDR gene (OMIM 601769) encodes
nuclear receptor and variations on the receptor,
which are caused by polymorphisms on the VDR
gene, can alter the response of the cells against
Vitamin D stimulation [20]. The aim of this case
report is to investigate the association between
polymorphisms of the VDR gene polymorphism
and its possible association with dentinogenesis
imperfecta type II in a Turkish family.
Material and method. Case Description. A
family with two (4 and 3 years olds, case I and II,
respectively) girls and one six years old boy, their
mother and father were referred to the Department
of Oral Diagnosis and Radiology, Faculty of
Dentistry, Marmara University with complaints of
sensitivity of their teeth. All family members were
healthy with no significant medical history. During
oral examination, teeth of affected girls and mother
were observed to have opalescence appearance
on transillumination (Fig. 1–3). The panoramic
radiographs confirmed the anomalies of the teeth
in question (Fig. 4, 5). Therefore, the patients were
referred to the Department of Pedodontics of the
same university.
During the clinical examination, teeth of case
I were observed to have attrition and have serious
enamel loss (Fig. 1) except second primary molars’s
occlusal surface. Panoramic radiograph of case I
revealed that all of the decidious teeth were affected
and have bulbous and obliterated pulp chambers
(Fig. 4). Her younger sister, case II, exhibited
yellowish discoloration (Fig. 2). No anomaly was
detected on the teeth of the 6-years-old brother but
it was observed that most of the teeth had decays
(Fig. 6). The youngest sibling was a baby (6-month-
old) and her teeth had not erupted yet.
The teeth of the mother were highly abraded. Her
panoramic radiograph revealed that all of the teeth
showed bulbous and obliterated pulp chambers,
and that root canals were dramatically reduced.
In addition, she had complaints of severe dental
sensitivity (Fig. 3, 5). All members of the family
denied other symptoms such as bone fragility or
hearing loss. According to the characteristic clinical
findings, DGI-II was diagnosed in this family.
VDR Genotyping. Informed consent was pro-
vided from all participants before taking part in
this study according to the Helsinki Declaration.
For the genetic analysis DNA was extracted
from buccal cells by using Quick Extract DNA
Extraction Solution (Epicentre, USA). The BsmI,
Fig. 1. Intraoral view of case I, revealing loss of enamel:
a – the maxillary; b – mandibular arch
Fig. 2. Intraoral view of the mandibular arch of case II
30
K. Ulucan, S. Akyüz, G. Özbay et al.
ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. Ò. 47. ¹ 5
TaqI and FokI polymorphisms of the VDR
gene was determined by PCR-RFLP method as
previously described [21]. Amplicons lacking the
restriction enzyme sites were donated as B, T and
F alleles, in contrast presence of the cutting sites
were donated as b, t and f alleles for BsmI, TaqI
and FokI polymorphisms, respectively.
For BsmI polymorphism, affected mother and
two children were bb whereas unaffected father and
child were Bb. For TaqI, one of the affected children
was tt whereas the rest were Tt (Fig. 7). All the
family members were FF for FokI polymorphism.
Discussion. Developmental defects of the human
dentition are not common and can adversely affect
the physical and psychological health of children.
In the present study, family with DGI-II was
examined in the view of medical history, clinical
evaluation, radiographic assessment and VDR poly-
morphisms.
In the family history, it was find out that youn-
ger sister, her mother, their relatives including aunts
and uncle had the same appearances in their teeth
but her older brother and her father, also paternal
family were not affected.
The enamel hypermineralization is independent
of extracellular hypocalcemia, so Zhang et al. [18]
theorized that vitamin D acts on local enamel
Fig. 3. Intraoral view of the dentitions, revealing serious
loss of enamel and vertical dimensions of mother
Fig. 4. Panoramic radiograph of case I: teeth with pulp
obliteration, bulbous crowns and short, malformed roots
Fig. 5. Radiographic evaluation of the affected mother
Fig. 6. Clinical evaluation of the unaffected 6-years of
brother
Fig. 7. Digestion profiles of VDR gene; a – by BsmI en-
zyme, M: 100 bp molecular marker; 1, 2: Heterozygous
genotype; 3: Mutant genotype; b – by TaqI enzyme, M:
100 bp molecular marker; 1–4: Heterozygous genotype;
5: Mutant genotype
31
Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI)
ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. Ò. 47. ¹ 5
mineralization. The direct action of vitamin D
on the target cells usually functions through
genomic and nongenomic pathways. Early enamel
mineralization may be secondary to the absence of
hormone-dependent VDR actions in ameloblasts.
In osteoblasts lacking VDR, Sooy et al. [22] re-
ported positive regulation of osteogenic potential.
The present study including the Turkish family
with DGI-II lets us consider the BsmI B allele
as a risk factor. Molecular mechanism of how
BsmI polymorphism affects VDR expression is still
unclear but the B allele was reported to have a
linkage with short PolyA formatting allele [23].
BsmI polymorphism is located in intron 8, near 3’-
UTR. Because the 3’ UTR may modulate mRNA
stability and degradation, this polymorphism was
reported to alter the level of mRNA [21]. Thus,
in our family, presence of B allele seems to play a
protective role for DGI-II and bb genotype can be
a risk factor for the formation of DGI-II.
TaqI polymorphism is located in exon 9 near
to 3’-UTR, and is believed to regulate PolyA
formation [23]. The molecular function of this
polymorphism is still unclear. In our family only
one of the affected children was tt, all the other
family members were Tt. We assume that this
polymorphism may cause DGI-II only with the
other accumulated mutation(s), not alone.
FokI polymorphism is located in exon 2 and has
a metabolic activity by having an important role in
transcriptional activation of VDR gene [21]. All of
the members were FF for the FokI polymorphism,
indicating that this polymorphism doesn’t have any
affect in formation of DGI-II, in the examined family.
Preventing the abrasion of the erupted tooth
and establishing an appropriate vertical dimension
are the outcomes of the proper treatment of this
condition. This treatment will enable clinicians to
preserve the function, aesthetics and normal growth
of the teeth. It was reported that individuals with
DI in primary dentition might not have DI in the
permanent dentition [24]. Severe DI can be treated
at two stages in deciduous teeth. If diagnosed early,
stage I is around 18–20 months and stage II is
28–30 months. This will be curbed at its onset
in deciduous dentition and pave the way for a
healthier permanent dentition [25].
Developmental defects of enamel and dentin are
frequently observed in the pediatric dental clinic.
In our cases, because of the ages of the children,
considered stainless steel crown restorations for
preventing tooth loss could not be applied. As
soon as the cooperation is gained, topical fluoride
applications can be made in every 6 months to
reduce sensibility.
Conclusion. This is the first report including
DGI-II and VDR FokI, TaqI and ApaI poly-
morphisms in a Turkish family. There may be
several SNPs effecting dentin and enamel deve-
lopment, polymorphisms of VDR are only one
of them. Although the exact mechanism of the
VDR polymorphisms is still unknown, bb geno-
type of BsmI polymorphism may be a causative
and diagnostic tool for DGI-II, alone or with
other gene alterations. The other polymorphisms
of VDR gene didn’t have any important affect
in the etiology of DGI-II in the examined Turkish
family.
K. Ulucan, S. Akyüz, G. Özbay,
F.N. Pekiner, A. lter Güney
ÈÇÓ×ÅÍÈÅ ÏÎËÈÌÎÐÔÈÇÌÀ ÃÅÍÀ
ÐÅÖÅÏÒÎÐÎÂ ÂÈÒÀÌÈÍÀ D (VDR) FokI,
TaqI È ApaI Â ÑÅÌÜÅ Ñ ÍÅÏÎËÍÛÌ
ÄÅÍÒÈÍÎÃÅÍÅÇÎÌ
Íåïîëíûé äåíòèíîãåíåç II òèïà (DGI-II) – ñîñ-
òîÿíèå, êîòîðîå íàñëåäóåòñÿ êàê àóòîñîìíûé äîìè-
íàíòíûé ïðèçíàê è õàðàêòåðèçóåòñÿ êàê àíîìàëü-
íàÿ ñòðóêòóðà äåíòèíà, êîòîðàÿ çàòðàãèâàåò ïåðâè÷-
íûé è âòîðè÷íûé ðîñò çóáîâ. Ãåíåòè÷åñêàÿ ýòèî-
ëîãèÿ çàáîëåâàíèÿ âñå åùå îñòàåòñÿ íåèçó÷åííîé,
íî ïðåäïîëàãàåòñÿ, ÷òî èìååò ãåíåòè÷åñêè ãåòåðî-
ãåííóþ îñíîâó. Öåëüþ ðàáîòû áûëî ñ ïîìîùüþ
PCR-RFLP îöåíèòü DGI-II è èçó÷èòü ñâÿçü ìåæäó
ïîëèìîðôèçìîì BsmI, TaqI è FokI ãåíà VDR è
íåïîëíûì äåíòèíîãåíåçîì II òèïà â îäíîé èç òó-
ðåöêèõ ñåìåé. Çàòðîíóòûå áîëåçíüþ ìàòü è äâå äî-
÷åðè áûëè ðåöåññèâíûìè ãîìîçèãîòàìè bb â îòíî-
øåíèè ïîëèìîðôèçìà BsmI, â òî âðåìÿ êàê çäîðî-
âûé ñûí è ìóæ áûëè ãåòåðîçèãîòàìè Bb. Ïî TaqI
ïîëèìîðôèçìó îäíà èç áîëüíûõ äî÷åðåé áûëà tt, à
îñòàëüíûå ÷ëåíû ñåìüè – Tt. Âñå ïåðå÷èñëåííûå
÷ëåíû ñåìüè áûëè FF ïî ïîëèìîðôèçìó FokI. Î÷å-
âèäíî, ïîëèìîðôèçì bb BsmI ñâÿçàí ñ DGI-II, îä-
íàêî íåîáõîäèìî èññëåäîâàíèå áîëüøåé âûáîðêè,
÷òîáû ñ÷èòàòü åãî ôàêòîðîì ðèñêà.
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Received 22.03.12
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/ENU (Use these settings to create Adobe PDF documents best suited for high-quality prepress printing. Created PDF documents can be opened with Acrobat and Adobe Reader 5.0 and later.)
>>
/Namespace [
(Adobe)
(Common)
(1.0)
]
/OtherNamespaces [
<<
/AsReaderSpreads false
/CropImagesToFrames true
/ErrorControl /WarnAndContinue
/FlattenerIgnoreSpreadOverrides false
/IncludeGuidesGrids false
/IncludeNonPrinting false
/IncludeSlug false
/Namespace [
(Adobe)
(InDesign)
(4.0)
]
/OmitPlacedBitmaps false
/OmitPlacedEPS false
/OmitPlacedPDF false
/SimulateOverprint /Legacy
>>
<<
/AddBleedMarks false
/AddColorBars false
/AddCropMarks false
/AddPageInfo false
/AddRegMarks false
/ConvertColors /ConvertToCMYK
/DestinationProfileName ()
/DestinationProfileSelector /DocumentCMYK
/Downsample16BitImages true
/FlattenerPreset <<
/PresetSelector /MediumResolution
>>
/FormElements false
/GenerateStructure false
/IncludeBookmarks false
/IncludeHyperlinks false
/IncludeInteractive false
/IncludeLayers false
/IncludeProfiles false
/MultimediaHandling /UseObjectSettings
/Namespace [
(Adobe)
(CreativeSuite)
(2.0)
]
/PDFXOutputIntentProfileSelector /DocumentCMYK
/PreserveEditing true
/UntaggedCMYKHandling /LeaveUntagged
/UntaggedRGBHandling /UseDocumentProfile
/UseDocumentBleed false
>>
]
>> setdistillerparams
<<
/HWResolution [2400 2400]
/PageSize [612.000 792.000]
>> setpagedevice
|