DISCUSSION between VDR gene polymorphism and the



Diabetes mellitus is an increasingly global health challenge including Saudi Arabia. It has been reported by
the World Health Organization (WHO) that Saudi Arabia has the second alarmingly increasing problem
of diabetes in the Middle East and the seventh in the world2.  It is likely that both hereditary and
environmental factors assume important role in the disease pathogenesis26.
Different research groups have studied a number of candidate genes that are likely to
induce the susceptibility to T2DM in various
populations. However, until now, 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 alter 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) area in
western Saudi Arabia.

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No significant difference was seen in the genotype distribution and
allele frequencies of both SNPs in FokI and BsmI polymorphisms in
VDR gene between the control and the patients with T2DM.  A critical factor for consideration in our
results on VDR polymorphisms is that, this research has been made in Makkah environs
of Saudi Arabia, an area that is known to have two seasonal variations, hot and
extremely hot (Table 3).  The available
sunshine throughout the year is fairly high and thus Makkah environs  can be
considered a unique
reference district for the possible bio-accessibility of vitamin D throughout
the year, unlike many European, North American and even areas in Asian
countries that are situated in the northern hemisphere such as Hokkaido region
of Japan.

Several researchers have studied the relationship of VDR
polymorphism in various populations. In Polish subjects, Malecki et al have
examined the polymorphism of four single nucleotide polymorphisms (SNPs) of VDR
gene (BsmI, TaqI, FokI and ApaI) and they found
that the genotype and allele distribution is the same in both controls and T2DM35.
 Additionally, in French Caucasian
population, Ye et al studied the same SNPs of VDR gene (BsmI, TaqI,
FokI and ApaI) and they observed that both the genotype and
allele distribution is the same in both controls and T2DM in36.   Besides,/
/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
association between VDR FokI polymorphism and T2DM and found no difference of
the genotype distributions and allele frequencies between T2DM subjects
and controls in Italians38.  Besides, in
Chinese Han subjects, 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 relationship between VDR FokI polymorphism and T2DM was
observed, Mahjoubi et al 40. Accordingly, all of the above previously
reported observations agree/ concur and bolster/ support our
results that the reported polymorphisms of VDR gene have no bearing on the diabetes

Strikingly, contrasting  results were
obtained by different investigators examining VDR variants and diabetes in
different geographical and environmental regions.  For instance, in North Indians (Kashmiri
population), Malik et al reported VDR TaqI and BsmI
polymorphism and they similarly, found that BsmI
G allele is associated with T2DM risk41. Likewise, in United
Arab Emirates, 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 subjects < 55 years old; Jia et al noted that FokI polymorphism is associated with T2DM43.  In Saudi population of Riyadh area/ region, Aldaghri et al examined the polymorphism of four SNPs in VDR gene (ApaI, FokI, TaqI and BsmI) and a relationship/ 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 district; which may, among other possibilities, be clarified by differences in the genetic background of the participants or because of some enigmatic environmental factors such as the daily exposure to sunlight and temperature variations. The present study has restrictions due to moderately modest  number of subjects. Further studies will be needed to assess the serological levels of the VDR and related metabolites and related genetic analysis in a large T2DM cohort with clinical information.  These investigations will be important basis to understand the role of VDR in the pathogenesis of T2DM in unique geographical and ethnic region. In conclusion, our investigations on the VDR gene polymorphisms in Makkah district diabetic patients clearly validate 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.