UNIVERSIDADE ESTADUAL PAULISTA
“JÚLIO DE MESQUITA FILHO”
Instituto de Ciência e Tecnologia
Campus de São José dos Campos
ORIGINAL ARTICLE DOI: https://doi.org/10.4322/bds.2024.e4184
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Braz Dent Sci 2024 July/Sept;27 (3): e4184
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Genetic variants of vitamin-D receptor genome and teeth caries
susceptibility in Iraqi children
Variantes genéticas do genoma do recetor de vitamina D e suscetibilidade à cárie dentária em crianças iraquianas
Haraa Khairi AL-HADITHI1 , Ghasaq Asim ABDUL-WAHAB2 , Maha Jamal ABBAS1 , Zaineb Amjed AL-NUAIMY3
1 - Mustansiriyah University, College of Dentistry, Pedodontics, Orthodontic and Preventive Dentistry Department. Baghdad, Iraq.
2 - Mustansiriyah University, College of Dentistry, Department of Oral Surgery and Periodontology. Baghdad, Iraq.
3 - Ajman University, College of Dentistry. Al-Ain, United Arab Emirates.
How to cite: Al-Hadithi HK, Abdul-Wahab GA, Abbas MJ, Al-Nuaimy ZA. Genetic variants of vitamin-D receptor genome and teeth caries
susceptibility in Iraqi children. Braz Dent Sci. 2024;27(3):e4184. https://doi.org/10.4322/bds.2024.e4184
ABSTRACT
Objective: To nd out if there is a link between the TaqI, ApaI, BsmI, and FokI polymorphisms of the vitamin
D receptor (VDR) and dental caries risk in Iraqi children. Material and Methods: The study had a sample of
one hundred children, consisting of fty males and fty females, their mean age of 10.2 ± 1.21 years old. The
study volunteers were categorized into two groups: a moderate caries risk group (DMFT, 1-4) consisting of
50 individuals, and a caries-free group including 50 individuals. Salivary samples were obtained from each
participant, and subsequent DNA extraction was performed. The VDR gene was geno-typed using the polymerase
chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. All data were subjected
to statistical analysis using the chi square test, Fisher’s exact test, and Odds ratios; results considered signicant
when (P<0.05). Results: A statistically signicant difference was seen in the frequency of FokI genotypes (CC)
between children with caries and those without caries (P<0.05). Individuals possessing the (CC) genotype had
a 2.745-fold higher probability of being susceptible to dental caries with CI 95% of (1.077 - 6.996). While there
were no signicant differences (P>0.05) found between the TaqI, ApaI, and BsmI genotypes and cavities in the
teeth. Conclusion: FokI (rs2228570) polymorphisms of the vitamin D receptor (VDR) showed an association
with dental caries. VDR genetic variants may be employed in the future as a potential marker for identifying
people at risk for caries when paired with environmental variables, as well as for caries prevention and treatment.
KEYWORDS
Caries; Gene; Genetic; Polymorphism; Vitamin D.
RESUMO
Objetivo: Descobrir se existe uma ligação entre os polimorsmos TaqI, ApaI, BsmI e FokI do recetor da vitamina
D (VDR) e o risco de cárie dentária em crianças iraquianas. Material e Métodos: O estudo teve uma amostra de
cem crianças, composta por cinquenta do sexo masculino e cinquenta do sexo feminino, com uma idade média
de 10,2 ± 1,21 anos. Os voluntários do estudo foram categorizados em dois grupos: um grupo de risco moderado
de cárie (CPO-D, 1-4), constituído por 50 indivíduos, e um grupo sem cárie, constituído por 50 indivíduos. Foram
obtidas amostras salivares de cada participante e subsequente extração de DNA. O gene VDR foi genotipado
utilizando a reação em cadeia da polimerase (PCR) e técnicas de polimorsmo de comprimento de fragmentos
de restrição (RFLP). Todos os dados foram submetidos a análise estatística utilizando o teste do qui-quadrado,
o teste exato de Fisher e Odds ratios; os resultados foram considerados signicativos (P<0,05). Resultados:
Foi observada uma diferença estatisticamente signicativa na frequência dos genótipos FokI (CC) entre crianças
com cárie e sem cárie (P<0,05). Os indivíduos que possuíam o genótipo (CC) tinham uma probabilidade 2,745
vezes maior de serem susceptíveis à cárie dentária com IC 95% de (1,077 - 6,996). Embora não tenham sido
encontradas diferenças signicativas (P>0,05) entre os genótipos TaqI, ApaI e BsmI e as lesões de cárie nos dentes.
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Braz Dent Sci 2024 July/Sept;27 (3): e4184
Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
INTRODUCTION
Dental decay is classied by World Health
Organization (WHO) as the ternary most
detrimental ailment to human well-being, right
after cancer and cardiovascular disease. Based on
these ndings, the decayed-missing-lled index
has exhibited a global drop due to advancements
in the field of stomatology. However, it is
important to note that dental caries continues to
adversely affects the physical characteristics and
overall well-being of a signicant proportion of
school-aged children, ranging from 60% to 90%,
as well as most adults [1].
Vitamin D has been recognized as a risk
factor for the occurrence and prevalence of dental
caries due to its involvement in two signicant
roles. It plays an essential function in the oral
cavity, especially in the mineralization of teeth
and antibacterial action through the stimulation
of antibacterial peptide secretion, as well as its
influence on “ameloblasts and odontoblasts”
cells in the creation of enamel and dentin
via the signaling pathways [2]. It is currently
understood that Vitamin D Receptor (VDR) in
many cells throughout the body, including those
in salivary gland, dentin and enamel forming
cells. The binding of vitamin D to its VDR, which
is a nuclear transcription factor, inuences the
activity of various genes that make up about
5-10% of the human genome. These genes are
involved in mineral metabolism, cell life cycle,
immune response, and energy metabolism,
resulting in genomic effects [3].
Vitamin D receptor is a ligand-dependent
transcription modulator which maps to
human chromosome 12q13.1; that facilitates
1,25 (OH)2 D3’s cytoplasmic distribution.
Its binding to the vitamin D receptor element
enables it to carry out several functions, such as
immune cell charatarization, bone mineralization,
improved homeostasis, its important in regulating
calcium and phosphorus metabolism, as well as
cell growth and differentiation. The biological
functionality of 1,25-dihydroxyvitamin D3 is
determined by its interaction with the ligand-
activated transcription factor [4].
Polymorphism refers to genetic variations
that occur in 1% or more of the population. Some
of these genetic variables produce or eliminate
restriction enzyme positions in DNA [5]. Thus,
restriction enzyme-digestion of DNA containing
these variants results in DNA fragments of varying
lengths and sizes, and these polymorphisms
are referred to as restriction fragment length
polymorphisms (RFLPs). The presence of single
nucleotide polymorphisms within the VDR gene
has been observed to have an impact on the
Taq-1, Apa-1, and Bsm-1 sites located in exons
8 and 9. Additionally, the Fok-1 site is inuenced
by a specific polymorphism that is situated
within exon 2 [6]. There is a growing body of
evidence suggests that hereditary elements may
be associated with caries susceptibility, and
genetic factors account for over 40% of caries
risk [7]. Identifying the susceptibility of the
host, i.e., the role of diverse genetic elements,
improves the willingness of specialist to clarify
the signicance of family history and hereditary
risk indicators in the development of disease [8].
Controlling caries will require the development
of new methods for identifying those who are at
a high risk. As observed in the previous studies,
host genetic variation, such as the Vitamin D
Receptor (VDR), may play a role in elevating
the susceptibility to the disease. Therefore, it is
crucial to investigate VDR gene polymorphisms
as a marker for identifying patients who are at a
high risk of developing caries [9,10]. A recently
published comprehensive study conrms that
there is a greater incidence of dental caries in
individuals with low levels of vitamin D, however
the connection with VDR gene receptors is still
uncertain. More investigations are required
to fully understand the complex relationship
between dental caries and vitamin D and its
receptor [11].
Here, we investigated in this case control-
study the relationship between polymophisms
Conclusão: Os polimorsmos FokI (rs2228570) do recetor da vitamina D (VDR) mostraram uma associação com
a cárie dentária. As variantes genéticas do VDR podem ser utilizadas no futuro como um potencial marcador
para a identicação de pessoas em risco de cárie quando emparelhadas com variáveis ambientais, bem como
para a prevenção e tratamento da cárie.
PALAVRAS-CHAVE
Cárie; Gene; Genética; Polimorsmo; Vitamina D.
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Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
in the VDR domain and its association with
predisposition to dental caries in salivary samples
of Iraqi children, using (RFLPs).
MATERIALS AND METHODS
Study Subjects: The study included a
sample of 100 children, with age range (8
to 10 years), who needed dental care at the
pedodontics and preventive department
of Mustansyriah University’s College of
Dentistry. The children selection was based
on specic criteria, mixed dentition (primary
and permanent) according to the age sample
(8-10) which involved experiencing pain due
to caries or seeking routine dental checkups.
The participants exhibited a state of good
health, as they did not present any systemic
disorders and were not consuming any
nutritional supplements. The participants
were given a sheet of information that
described every aspect of the study and the
use of saliva samples. Saliva samples were
taken subsequent to an oral examination.
In addition, the DMFT (D: decayed, M:
missing, F: lled, T: tooth for permanent
teeth) and dmft (d: decayed, m: missing, f:
lled, t: tooth for deciduous teeth) indices
were recorded according to WHO criteria
1997 [12] and all children were classied
according to the DMFT scores into:
Group-1 (Control group): caries-free
(dmft/DMFT=0): This group consists of
individuals who have no dental caries,
no teeth missing due to caries, and no
fillings. A DMFT score of 0 indicates
that the person has not experienced any
tooth decay or required any restorative
dental treatments. This group represents
the baseline or ideal oral health status in
the study.
Group-2 (Patients group): with moderate
caries (dmft/DMFT=1-4): This group
includes individuals who have a DMFT
score ranging from 1 to 4. This means
they have experienced one to four
instances of dental caries, missing teeth
due to caries, or lled teeth. The DMFT
index of 1-4 indicates a moderate level
of caries risk, signifying some degree
of dental health issues but not severe
enough to be classified as high risk
(which would typically have a higher
DMFT score).
Ethical aspect of the study
The study was authorized by Mustansiriyah
University’s Ethics committee with REC reference
REC131, study number MUPREV202301; and
according to the principles of the Declaration of
Helsinki. Subjects’ rights have been protected
after receiving written informed consent from the
parents of the children to use their information’s
and saliva for dental research purposes.
Sample Size was calculated at 95%
condence interval with a 5% error margin using
the online program EPITOOLS (https;//epitools.
ausvet.com.au/casecontrolss).
Name, age, residence, and habits have all
been requested for each patient. All individuals
had identical environmental exposures.
In the dental clinic, examinations were
carried out on dental chairs, using dental mirrors
and sharp dental explorers. The examinations of
occlusal and interproximal surfaces of the teeth
were carried out under articial lights. Teeth that
were decayed, missing, due to caries, or lled
were recorded according to the modied World
Health Organization 1997 caries diagnostic
criteria. The Numbering System approach was
used to examine the teeth. Starting with the last
upper right molar, the examination proceeded in
a systematic manner from one tooth to the next
neighboring tooth until the upper left last molar
was reached. Next, the lower left last molar was
examined, followed by the lower last right molar.
The process was repeated until all the teeth in the
mouth had been examined. Caries examination
and diagnosis were performed by two dentists,
and examination consistency was certied by
examining 30 children before the initiation of
the study.
Saliva Sample Collection: Saliva samples
that had not been stimulated were obtained by
following the steps outlined in the Navazesh
protocol [13]. Before the sample collection, the
participants were instructed to avoid brushing;
abstain from eating and drinking for a period
of two hours. The samples were taken between
the hours of 10:00 and 11:00 in the morning.
In order to keep the participants relaxed and
stress-free during the whole process of collecting
samples, a regular chair was used instead of a
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Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
dental chair to seat them. After the un-stimulated
saliva had accumulated in the mouths oor, a
volume of 5 milliliters was taken and placed in
the saliva collecting tube. The samples of saliva
were centrifuged, and the supernatant that was
produced was chilled to a temperature of - 4°C
for further analysis.
Salivary DNA Isolation: Salivary DNA
was isolated according to the manufacturer’s
instructions utilizing a reagent that is
commercially-available (Salivary DNA Isolation
reagent, Norgen \ Biotek, Canada)). The DNA
quantity in each sample was measured by a
spectrophotometer and afterwards kept at a
temperature of -20°C until further analysis was
conducted.
Single Nucleotide Polymorphism Selection
and Geno-typing: The VDR SNP was chosen
after reviewing the literature and retrieved from
NCBI “(https://www.ncbi.nlm.nih.gov)”. To
determine the RFLP, the amplication of DNA
was achieved using polymerase chain reaction
(PCR) technique, followed by digestion with a
specic restriction enzyme. The following primer
pairs are listed in (Table I) for amplifying the DNA
anking of SNPs.
PCR (RFLPs) assay
The PCR mixture, with a volume of 25 μl,
was composed of various components. These
included 10mM TrisHCl, 200 μM dNTPs, 20 pmol
of each primer, 1.5mM MgCl2, 0.5 units of Taq
polymerase (F enzyme) and 50 to 100 nanograms
of DNA to use as a template. The cyclic pattern
can be described as follows: The thermal cycling
procedure encompassed an initial denaturation
stage at a temperature of 94°C for a duration of
5 minutes, continued by 35 cycles of amplication.
The experimental procedure involved a series of
cycles, with each cycle including a denaturation
phase at 95°C heating for 60 seconds, followed
by an annealing step at 68°C for 60 seconds, and
with an extension step at 72°C for a period of
2 minutes. The nal extension step for 7 minutes
was performed at 72°C. A 10 microliter amount
of the polymerase chain reaction (PCR)-amplied
product was submitted to enzymatic digestion
using restriction enzymes at a temperature of
37°C for an overnight duration. The digested
product was then brought into view by running it
on an ethidium bromide-stained 3% agarose gel.
Statistical Analysis
The study results presented using several
statistical measures, such as frequency (expressed
as a percentage), mean, and standard deviation.
The chi-square test, variance analysis, and t-test
were utilized for making comparisons. Odds
ratios and 95% condence intervals (CIs) were
calculated. The p-value for Hardy-Weinberg
equilibrium (HWE) was assessed using the chi-
squared test, P< 0.05 was considered a signicant
divergence from HWE.
Statistical comparisons were conducted
using SPSS software (version 23; IBM SPSS Corp,
Armonk, NY, USA).
RESULTS
The average age of the study participants
was 10.2 1.21 years. The control group consisted
of children with no evidence of caries (DMFT
= 0; n = 50; 25 boys and 25 girls), whereas
the patient group consisted of children with
intermediate caries risk (DMFT = 1-4; n = 25
boys and 25 girls).
The distribution of genotypes at four
polymorphic loci in selected genes among caries-
free subjects and patients with caries is shown in
(Table II).
In order to show the significance of the
association between various SNP genotypes and
caries status in the case and control groups, odds
ratios were calculated too.
Table I - Primers for VDR Gene Polymorphisms
VDR SNPs Primers
Taq-I (rs 731236) exon 9 (T > C) F: “5- CAG AGC ATG GAG AGG GAG CAAG-3” R: “5- GGA TGT ACG TCT GCA GTG TG -3”
Apa-I (rs 7975232) intron 8 (G > T) F: “5- CAG AGC ATG GAC AGG GAG CAAG-3” R: “5-CAC TTC GAG CAC AAGGG CGTTAG-3”
Bsm-I (rs 1544410) intron 8 (G˃A) F: “5-CAA CCA AGA CTA CAA GTA CCG CGT CATGA -3” R: “5- AAC CAG CGG GAA GAG GTC
AAG GG -3”
FOK-I (rs 2228570) exon 2 (T > C)
(rs 10735810) 2 SNPs
F: “5- AGC TGG CCC TGG CAC TGA CTC TGG CTC -3” R:“3- ATG GAA ACA CCT TGC TTC TTC TTC
TTC CTC-5”
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Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
The genotype CC of (rs2228570)
demonstrated a signicant association with tooth
decay (P = 0.027), indicating that individuals with
this genotype had a 2.745-fold higher risk of active
caries (OR = 2.745 95% CI = [1.077 - 6.996]).
On the other hand, the VDR polymorphisms
ApaI, TaqI, and BsmI were found to have no
signicant association with tooth decay. The odds
ratios (OR) and corresponding 95% condence
intervals (CI) for ApaI, TaqI, and BsmI were as
follows: ApaI (OR = 0.419, 95% CI = [0.157 -
1.118], p = 0.051), TaqI (OR = 0.592, 95% CI =
[0.224 - 1.564], p = 0.548), and BsmI (OR =
0.635, 95% CI = [0.239 - 1.685], p = 0.680), as
shown in Table II.
The C and T allele frequencies of FokI
and ApaI polymorphisms were substantially
different between caries-experienced and caries-
free groups (p = 0.005, 0.047, respectively).
Interestingly FokI have a 2.7-fold increased
likelihood of developing active caries (odd ratio =
2.745, with a 95% condence interval = 1.077 -
6.996, P-value = 0.026).
Whereas no signicant differences were seen
in the genotypes and allele frequencies of TaqI
and BsmI polymorphisms between persons with
dental caries and those without dental caries.
(Table III).
All the VDR SNPs were not in Hardy-
Weinberg equilibrium in unaffected and affected
individuals, except for rs 7975232 (ApaI) in
patients’ group (P=0.077) and rs 1544410 (BsmI)
in control group (P=0,064) were in agreement
with HWE (Table IV).
DISCUSSION
Based on earlier research, the development
of dental caries has been linked to a variety of
variables. Genetic factors may play a signicant
role in the multifactorial character of dental
caries, although their involvement in caries
development has not been well investigated [14].
Dental caries can be caused by a complicated
combination of heredity and environmental
factors [15]. Furthermore, it has been determined
that hereditary factors contribute to almost
40% of the overall risk associated with caries
development [16]. Based on the findings of
published studies, the risk of dental caries can
be inuenced by both genetic and environmental
factors. These environmental factors include oral
hygiene, diet, bacteria, and host factors [17,18].
Vitamin D has a crucial role in maintaining
calcium homeostasis, as well as modulating
the immunological response and exerting
anti-inammatory effects [19]. The VDR gene
facilitates the physiological role of the vitamin D
metabolite, which is linked to the regular growth
of tooth enamel [20,21]. Genetic variations in
the vitamin D receptor (VDR) within people have
been found to result in defects and morphological
diversity in tooth enamel [22].
In the present case-control research, we aim
to determine the potential connection between
four VDR gene variants (TaqI, ApaI, BsmI,
Table II - Genotype Distribution of Four VDR Polymorphisms in Study Groups
Genotype Caries group No.50 Control group No. 50 Odd ratio 95% CI *Χ2P- Value
ApaI
(rs 7975232) G>T
GG 21 (42%) 16 (32%) Referent - -
GT 18 (36%) 14(28%) 0.979(0.377 - 2.544) 0.735 0.391NS
TT 11 (22%) 20(40%) 0.419(0.157 - 1.118) 3.786 0.051NS
TaqI
(rs731236) T>C
TT 15 (30%) 10 (20%) Referent - -
TC 11(22%) 13(26%) 0.564 (0.181- 1.752) 0.219 0.639NS
CC 24 (48%) 27(54%) 0.592 (0.224-1.564) 0.360 0.548NS
FOKI
(rs 2228570) T>C
TT 12 (24%) 20 (40%) Referent - -
TC 10 (20%) 13(26%) 1.282(0.430-3.819) 0.508 0.475NS
CC 28 (56%) 17(34%) 2.745(1.077 - 6.996) 4.888 0.027S
BsmI
(rs 1544410) G>A
GG 17(34%) 12 (24%) Referent - -
GA 15(30%) 18(36%) 0.588(0.214- 1.611) 0.407 0.523NS
AA 18(36%) 20(40%) 0.635(0.239 - 1.685) 0.169 0.680 NS
No: Number. *chi-squared test. S: Significant. NS: Non-Significant.
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Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
and FokI) and dental caries in Iraqi children.
Individuals with the CC genotype of VDR
polymorphisms FokI have a 2.7-fold increased
likelihood of developing active caries (odd ratio
= 2.745, with a 95% condence interval = 1.077
- 6.996, P-value = 0.026).
We found a definite correlation between
active caries and the Fok1 in VDR CC genotypes.
This discovery may be used to determine
how hereditary immunological deficiencies,
inammatory alterations, and host vulnerability
affect a person’s risk of developing caries. Due to
the existence of FokI polymorphic gene at the
gene’s start site (start codon) may result in the
production of vitamin D proteins of various
sizes that could significantly affect the caries
vulnerability in study samples.
Yu et al. did comparable research in the
Chinese population that conrmed our results,
and this SNP was shown to have a substantial
connection with dental caries in permanent
dentition. The incidence of the TT genotype and
T allele was considerably lower in the patient
group compared to the caries-free control group,
whereas the CT and CC genotypes were more
prevalent in the patient group [23].
The meta-analysis investigated the correlation
between several single nucleotide polymorphisms
(SNPs) in the VDR gene and dental caries. Among
all the SNPs analyzed, only the Fok1 SNP exhibited
a statistically signicant link with dental caries.
Possible explanations for this result include the
location of the Fok1 SNP and its interaction with
co-transcription variables [20]. Das et al. carried
out a study with the intention of determining the
frequency of the Fok1 and Taq1 polymorphisms
in restriction fragment length (RFLPs) in the
vitamin D receptor (VDR) gene among a group of
healthy people living in India, as well as examining
any potential associations between these genetic
Table III - Allele Frequency of Four VDR Polymorphisms among Study Groups
Allele Frequency Caries group No.50 Control group No. 50 Odd ratio 95% CI *Χ2P- Value
ApaI
(rs 7975232) G>T
G 60 (60%) 46(46%) Referent - -
T 40 (40%) 54 (54%) 0.5679(0.324 -0.995) 3.934 0.047S
Total 100 100
TaqI
(rs731236)T>C
T 41 (41%) 33(33%) Referent - -
C 59 (59%) 67(67%) 0.708(0.398 - 1.261) 1.3728 0.241NS
Total 100 100
FOKI
(rs 2228570) T>C
T 34 (34%) 53(53%) Referent - -
C 66 (66%) 47(47%) 2.189(1.237- 3.872) 7.735 0.005S
Total 100 100
BsmI
(rs 1544410) G>A
G 49(49%) 42(42%) Referent - -
A 51(51%) 58(58%) 0.753(0.431- 1.316) 0.988 0.320NS
Total 100 100
S: Significant. NS: Non-Significant. *: Chi-squared test.
Table IV - Hardy-Weinberg equilibrium for VDR polymorphisms
VDR SNPs HWE Caries group No.50 Control group No. 50
ApaI (rs 7975232)G>T HWE X2 value 3.125 9.521
P value 0.077 NS 0.002S
TaqI (rs731236)T>C HWE X2 value 14.865 8.488
P value 0.0001S0.0035S
FOKI (rs 2228570) T>C HWE X2 value 15.366 11.429
P value 0.0000HS 0.0007HS
BsmI (rs1544410) G>A HWE X2 value 7.990 3.408
P value 0.004 S0.064 NS
S: Significant. NS: Non-Significant. HS: Highly Signficant.
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Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
variations and levels of 25-hydroxyvitamin D.
A substantial correlation was seen between the
Taq1 restriction fragment length polymorphism
(RFLP) and levels of 25-hydroxy vitamin D.
However, no such correlation was found with the
Fok1 RFLP [24]. In different research that was carried
out on adults, it was discovered by Nireeksha et al.
that the T allele of rs-2228570 was substantially
related with the active caries condition [25].
Barbosa and colleagues carried out a study on
permanent dentition of Brazilian children (8 to
11 years old) in order to look into the connection
between Fok1 RFLPs in VDR and dental caries.
The results of the study suggested that there was
no correlation between the two variables that could
be considered statistically signicant suggesting the
limitation of their study is the fact that dental caries
was evaluated only with clinical examination and
some interproximal caries might not be detected
without radiographic examination also different
clinical scale was used to detect dental caries [14].
In contrast, our study revealed a substantial
association between individuals carrying the VDR
polymorphism ApaI T allele with a caries-free
status. However, no signicant associations were
seen between tooth decay and the TaqI and BsmI
polymorphisms. The ndings of this study are
consistent with other research conducted by Qin
et al, Izakovicova Holla et al and Kong et al, all of
them reported no signicant correlation between
the TaqI VDR polymorphism and the likelihood
of developing dental caries [10,26,27].
Contrarily, our research outcomes did not align
with the study conducted by Hu et al., since their
ndings demonstrated a substantial relation between
TaqI VDR polymorphism and the vulnerability
to dental caries among Chinese individuals [28].
Additionaly; the study carried out by Cogulu et al.
(2016) revealed that the TaqI genotypes present
in the VDR gene have the potential to serve as a
diagnostic indicator for assessing the predisposition
of Turkish children to dental caries [29].
Hardy-Weinberg equilibrium (HWE)
was used to calculate the expected common
homozygotes, expected heterozygotes, expected
rare homozygotes and states that the genotype
and alleles frequencies in a population will remain
constant from generation to generation in the
absence of other evolutionary inuences; thus,
the deviation from HWE equilibrium means that
something is occurring possibly evolution [30].
The discrepancy between our results and those
of other case control studies may be attributable to
the distinction between primary and permanent
dentitions, as well as the different methodological
approaches utilized, the geographical and ethnic
differences and the small sample size. More
well-conducted studies with larger sample sizes
are needed to investigate other factors that may
inuence the current suggested model, as well as
the association between VDR gene polymorphisms
and the risk of dental caries in both children and
adult patients with high caries risk.
CONCLUSION
This study designated that FokI (rs2228570)
gene polymorphism was related with increased
risk to dental caries. This conclusion highlights
the importance of genetic polymorphisms which
give the opportunity to clinicians to provide
patients with a through perception of their
proneness to dental caries in order to advocate
effectual oral hygiene measures for controlling
dental caries. This study spotlight on the fact that;
in spite of the various causes of dental decay;
subject susceptivity to caries is an crucial concern.
Acknowledgements
The authors would like to thank Mustansiriyah
University (www.uomustansiriyah.edu.iq)
Baghdad- Iraq for its support in the present work.
Author’s Contributions
GAAW, MJA: Conceptualization. HKAH,
GAAW, MJA: Methodology. GAAW: Formal
Analysis. GAAW, ZAAN: Data Curation. HKAH:
Software. HKAH:Validation. HKAH: Investigation.
HKAH: Resources. GAAW: Writing – Original
Draft Preparation. HKAH, MJA, ZAAN: Writing
– Review & Editing. HKAH, MJA: Visualization.
GAAW, MJA: Supervision. GAAW: Project
Administration Authorship.
Conict of Interest
The authors declare that they have no
conicts of interest related to this study.
Funding
None.
8
Braz Dent Sci 2024 July/Sept;27 (3): e4184
Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
Regulatory Statement
This study protocol was reviewed and
approved by MUCOD (College of Dentistry
Research Ethics Committee). It meets the
requirements of the current Human Research
Guidelines and full ethical approval has been
granted under the reference number REC131.
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9
Braz Dent Sci 2024 July/Sept;27 (3): e4184
Al-Hadithi HK et al.
Genetic variants of vitamin-D r eceptor genome and teeth caries susceptibility in Iraqi chil dren
Al-Hadithi HK et al. Genetic variants of vitamin-D receptor genome and teeth
caries susceptibility in Iraqi children
Ghasaq Asim Abdul-Wahab
(Corresponding address)
Mustansiriyah University, College of Dentistry, Pedodontics, Orthodontic
and Preventive Dentistry Department, Baghdad, Iraq.
Email: ghasaq.a.abdulwahhab@uomustansiriyah.edu.iq
Date submitted: 2023 Dec 08
Accept submission: 2024 Sept 16
