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INTRODUCTION  

Diabetes 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.

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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 investigated 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. 

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