DISCUSSION have studied several genes that may induce
June 10, 2019
Diabetes mellitus is a common and serious public health problem all
over the world involving Saudi Arabia. It has been reported by the World Health
Organization (WHO) that Saudi Arabia has the second highest rate of diabetes
among the countries of the Middle East and the seventh in the world2.
It is likely that both environmental and
genetic factors play important role in the pathogenesis of diabetes26.
Various research groups have studied several genes that may induce the
susceptibility to T2DM in different ethnicities. However, relatively fewer
studies have been conducted in Saudi Arabia to study the relationship between
VDR gene polymorphism and the susceptibility to T2DM. VDR
gene mediates transcription function, and the interaction with its
ligand (vitamin D) is known to affect insulin secretion and insulin function34.
We have investigated VDR FokI and
BsmI gene polymorphisms in a group of Saudi people with T2DM, and
matched control subjects for gender and age in Makkah (aka: Mecca) region in
western Saudi Arabia.
The result of this study found no significant difference in the genotype
distribution and allele frequencies of both FokI and BsmI polymorphisms
in VDR gene between the control and the patients with T2DM. An important factor for consideration in our
results on VDR polymorphisms is that, this study has been made in Makkah
environs of Saudi Arabia, a region that
is known to have two seasonal variations, hot and very hot (Table 3). The available sunshine through the whole year
is fairly high and thus Makkah region can be considered a special reference
region for the possible bio-availability of vitamin D throughout the year,
unlike many European, North American and even areas in Asian countries that are
located in the northern hemisphere such as Hokkaido area of Japan.
Several researchers have investigated VDR polymorphism in different
populations. In Polish subjects, Malecki et al have studied BsmI,
TaqI, FokI and ApaI gene polymorphisms of VDR gene and
they found that the genotype and allele distribution is the same in both controls
and T2DM35. Also, in French
Caucasian population, Ye et al studied the same SNPs of VDR gene (FokI,
BsmI, TaqI, and ApaI) and they observed that both the
genotype and allele distribution is the same in both controls and T2DM in36. Furthermore,
in Turkish population, Dilmec et al found no significant difference in
genotype and allele frequencies of the same four SNPs (BsmI, TaqI,
FokI and ApaI) of the VDR gene between both controls and T2DM37.
Among European Caucasians, Bertoccini
et al studied the VDR
FokI polymorphism in T2DM and found no difference of the genotype distributions
and allele frequencies between T2DM subjects and controls in Italians38.
Similarly, in Chinese Han population, Fei
Yu et al studied four VDR SNPs and found that VDR FokI and BsmI
polymorphism is not related to T2DM risk in Chinese39. In the African
continent, for Tunisian subjects, no significant association between VDR FokI
polymorphism and T2DM was observed, Mahjoubi et al 40. Thus, all
of the above previously reported observations concur and support our results that
the reported polymorphisms of VDR gene have no bearing on the diabetes
Interestingly, quite the opposite results were obtained by other
investigators studying VDR variants and diabetes in different geographical and
environmental regions. For example, in North
Indians (Kashmiri population), Malik et al reported VDR TaqI and BsmI
polymorphism and they also found that BsmI G allele is associated with
T2DM risk41. Similarly in United Arab Emirates population, Safar et
al found that the G allele and GG genotype of FokI and T allele and
TT genotype of BsmI are associated with T2DM risk in Emirati population42. Among the Chinese Han population < 55 years of age; Jia et al reported that FokI polymorphism
is associated with T2DM43. In
Saudi population of Riyadh region, Aldaghri et al studied the
polymorphism of four SNPs in VDR gene (ApaI, FokI, TaqI
and BsmI) and an association of BsmI T allele and C/T genotype
and TaqI A/G genotypes and T2DM was observed 31. These
findings differ from our observations in Makkah region; which may, among other
possibilities, be explained by differences in the genetic background of the
participants or due to
some unknown environmental factors such as the daily exposure to sunlight and
temperature variations. The present
study has limitations due to relatively small number of subjects. Further
studies will be needed to evaluate the serological levels of the VDR and
related metabolites and related genetic analysis in a large T2DM cohort with
clinical data. These investigations will
be important basis to understand the role of VDR in the pathogenesis of T2DM in
special geographical and ethnic region.
In conclusion, our studies on the VDR gene polymorphisms in Makkah
region diabetic patients clearly confirm similar studies in diverse ethnic
populations in Tunisian, and Chinese subjects that the FokI and BsmI
polymorphisms in the VDR gene show no significant difference in genotype and
allele frequency between controls and patients with T2DM. These data strongly
suggest that the FokI and BsmI SNPs may not contribute to the
susceptibility to T2DM among Saudi population.
The authors thank Dr. Abdulrahman Yousuf for his technical support
in the research laboratory in Faculty of Dentistry, Um Al-Qura University.
CONFLICT OF INTEREST
The authors declare that no conflict of interest
This study was funded by the Vice deanship for research,
Um Al-Qura University, Makkah, Saudi Arabia (No. 43309017).
List of Supporting Information:
No appendix is presented.