VITAMIN D RECEPTOR POLYMORPHISMS
AMONG THE TURKISH POPULATION
ARE ASSOCIATED WITH MULTIPLE SCLEROSIS
Bulan B1, Hoscan AY1, Keskin SN1, Cavus A1, Culcu EA1, Isik N2, List EO2, Arman A*4
*Corresponding Author: Dr. Ahmet Arman, The Department of Medical Genetics, Marmara Teaching
and Research Hospital, Marmara University, 34899, Pendik, Istanbul/TURKEY. Tel #: +90-216-
657 0606, Fax #: +90-216-414 47 31, e-mail: ahmetarman@marmara.edu.tr, ORCID Id: https://orcid.org/0000-0001-5547-0024
page: 10
|
|
DISCUSSION
MS is an immune mediated chronic inflammatory
demyelinating disease of CNS. While very little is known
about the etiology of this disease, vitamin D as well as
its receptor gene, VDR, are thought to be associated with
MS. However, this is a controversial topic since there is
disagreement in the literature. Therefore, we have evaluated
the polymorphisms in the vitamin D receptor (VDR)
among 271 MS patients and 203 healthy controls to determine
if we observed any association with it and MS in
the Turkish population. Our results showed a significant
relationship in the Turkish population between VDR gene
polymorphisms among MS or MS subtypes. This was true
for two distinct (Fok-I and Taq-I) VDR gene polymorphisms.
However, there was no significant relationship
between VDR gene Bsm-I polymorphism with MS or MS
subtypes in our study.
Previous research evaluating the effect of exogenous
vitamin D in prevention of MS development based on
genetic tendency has helped to establish the importance
of polymorphisms [22]. The Fok-I polymorphism is a T/C allele variation located in exon 2 which is in the translation
initiation site of VDR. An interaction was observed
between the dietary intake of vitamin D and the VDR Fok-I
polymorphism and risk of MS. It was argued that vitamin
D has a higher effect on MS prevention in women carrying
the T allele [22]. Therefore, the determination of immune
status by genetic predisposition, according to vitamin D
intake, allowed for better assessment of MS risk [22].
However, there was no association between Fok-I polymorphisms
on the VDR gene and MS in the Australian
population [25]. In a separate study evaluating MS patients
in the British population, there is a tendency for low VDR
expression in people with the Fok-I polymorphism (T/T)
genotype on the VDR gene. However, the relationship
between MS and VDR single nucleotide polymorphisms
has not been established, as results in the studies differ
from each other [29]. Smolders et al. observed a relation
between the Fok-I polymorphism in the VDR gene and
the level of vitamin D. The C allele of the Fok-I polymorphism
is associated with decreased 25(OH)D and
increased 1,25-dihydroxyvitamin D (1,25(OH)D) levels
[29]. Polymorphisms in the VDR gene were found to be
associated with the severity and course of MS, as Mamutse
et al. demonstrate that the Fok-I allele was associated with
a decreased 10 year disability level, following initial disease
development [30]. By contrast, a meta-analysis [22,
23, 25, 29, 31, 32] conducted on the Caucasian population
indicates that the risk of MS is independent of Fok-I
polymorphisms in dominant, heterozygote and recessive
gene models [7]. Another study found that distribution of
the VDR gene Fok-I polymorphisms was associated with
MS in the Turkish population [33]. In a meta-analysis
covering the research up to 2019, there was no association
found between Fok-I polymorphisms and MS [34]. In our
study, it was found that the Fok-I T/T polymorphism on
the VDR gene in a dominant inheritance model and Fok-I
T allele frequency were significantly associated with MS
in Turkish population.
The Bsm-I polymorphism is located in intron 8 of
VDR and has a G/A variation. The first studies to report
a relationship between MS and Bsm-I polymorphisms on
the VDR gene were found in the Japanese population [14,
24]. However, it was later found that there was no association
between Bsm-I polymorphisms on the VDR gene and
MS in the Canadian population [35]. In the meta-analysis
of studies up to 2019, there was no association between
Bsm-I polymorphisms and MS, but when compared with
the European population and the Asian population, there
was an association between Bsm-I polymorphisms and MS
[34]. In our study, it was found that there was no association
between Bsm-I polymorphisms on the VDR gene and
MS in the Turkish population.
The Taq-I polymorphism is found at exon 9 of VDR
with a C/T variation. An association was found between the
Taq-I polymorphisms on the VDR gene and MS in the Australian
population [25]. In contrast to this study, there was
no association between the Taq-I polymorphisms and MS
in the Canadian population [35]. A similar study found that
there was no association between Taq-I polymorphisms on
the VDR gene and MS in the Turkish population [33]. The
aforementioned meta-analysis includes the research on this
subject until 2019, and there was an association between
Taq-I polymorphisms and MS only in the heterozygote
model, but not in other inheritance models [34]. The results
of our study showed that Taq-I C/C polymorphism on the
VDR gene in dominant, homozygote and heterozygote inheritance
models, and C allele frequency were significantly
associated with MS in the Turkish population. In summary,
we found that a significant relationship in the Turkish population
exists between VDR gene polymorphisms (Fok-I,
and Taq-I) and MS. A similar study among the Turkish
population found an association between VDR gene Fok-I
polymorphisms and MS. According to this study, however,
there was no association between Taq-I VDR gene
polymorphisms and MS. These data are important, since
previous reports on this topic differ from one another, and
more studies are needed. Some of the limitations of our
study which should be considered include: small sample
size and a different ethnicity, compared to other studies.
These limitations might be the reason for the contradictions
between our study and the study of Kamisli et al. among
the Turkish population. Accordingly, our study adds further
evidence to the argument that VDR is associated with MS,
at least in certain populations.
Acknowledgements
This work was supported by the grant from The Marmara
University Research Foundation.
Declaration of Interest
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of
this article.
Author Contributions
BB: conducted the experiments and analyzed the
data; HAY: conducted the experiments and developed
the methodology; KSN: developed the methodology and
provisioned the materials;
CA: developed the methodology and provisioned the
materials; CEA: provisioned the materials; IN: provisioned
the materials; ELO: prepared the published work; AA:
planned, executed the research and prepared the published
work.
|
|
|
|
 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
