INTRODUCTION thereby applying preventive measures is the initial


mellitus (DM) is a serious world medical issue including Saudi Arabia1, 2.
 Little is known about the reason of T2DM;
nevertheless many of its risk factors have been recognized and are researched. T2DM,
as other inflammatory disease may be averted if its risk factors are detected during
early onset of the disease, and managed3-6.  Accordingly a comprehension of T2DM risk
factors and thereby applying preventive measures is the initial phase in
prevention, as this  will enable T2DM
patients to settle on the informed decision that prompts a sound lifestyle7,8.
In Saudi Arabia, there are moderately few studies directed to decide and assess
the T2DM risk factors in the Saudi populace and preventive measures9.

It is
well known that environmental conditions and genetic factors both assume
contributory parts in the development of T2DM.    in spite of the fact that the hereditary
factors assume a basic part in different types of diabetes mellitus, how the legacy
of these hereditary loci contributing to the disease remains obscure.   Besides, such hereditary components  may likewise cooperate with environmental
factors, for example, diet and atmospheric temperature10,11.  In general, predominantly, T2DM and T1DM are
polygenic conditions; however, several monogenic forms of diabetes have been
identified12.  Such identified
genes are assembled  into various
classifications, for example, those involved in control of growth factors, those
mediating signal transduction, and those associated with energy metabolism and
energy utlization13. Various
studies have been carried out on the relationship between the genetic variation
and diabetes; these studies require affirmation in various racial and ethnic
groups and environmental conditions14,15.

The gene of the VDR  is
exceedingly poly-morphic and is situated on chromosome 12q12-14. There are six commonly
researched VDR polymorphisms are: FokI polymorphism in exon 2; BsmI,
Tru9I, and ApaI polymorphisms situated between exons
8 and 9; the TaqI polymorphism present in exon 9; and the poly-A
polymorphism downstream of the 3´ un-translated region16,17.  The contribution of vitamin D in the development of T1DM has been researched
in several studies, and it was demonstrated that children whose diets were
supplemented with vitamin D have a lower incidence of T1DM in adulthood18.   Furthermore, abnormal vitamin D and calcium homeostasis likewise
contributes in the development of T2DM. 
High vitamin D status in subjects have been shown to provide protection
against T2DM19,20.  


Vitamin D
Receptor (VDR) is a member of the steroid-thyroid hormone receptor family21.  Vitamin
D is assumed to be an imperative part of the control of the endocrinal functions
of pancreas, particularly in the secretion of insulin22. The action of vitamin D
is mediated through association to its specific nuclear receptor (VDR) which is
expressed in beta (?)-cells21. Insulin
secretion from the beta (?)-cell is directed by Vitamin D and its receptor complex.
Moreover, Vitamin-D inadequacy decreases insulin synthesis and secretion in
humans and in animal models of diabetes and vitamin
D supplement in diet may increase the insulin secretion23,24. Polymorphism
has been depicted in the VDR genomic sequences that are able to modify the
activity of VDR protein25.  Despite the fact
that genetic basis of T2DM is still poorly understood, several studies
suggested that the VDR gene is a novel candidate gene contributing to the
susceptibility to the diabetes and particularly T2DM26-30.  

In this study, we
planned to investigate the relationship between VDR gene FokI and BsmI
polymorphisms and the risk of T2DM among Saudi people in Makkah region and its
environs.  Few studies about gene polymorphism
of VDR gene in T2DM have been conducted in Saudi Arabia31. In this
manner, it is important to affirm the relationship between VDR
polymorphism and the susceptibility of T2DM in Saudi subjects.