chapter  11
18 Pages

Nutritional Genomics of Vitamin D on Cardiovascular Disease

Micronutrients are substances required in small amounts, typically 5-10 micrograms daily, for proper functioning of the human body. Vitamins are one class of micronutrients, which cannot be synthesized in sufcient quantities within the body and therefore must be obtained exogenously. Of these, vitamin D, a fat-soluble vitamin can be synthesized in the human skin but is virtually absent from most natural foods (Wang 2009) with the exception of amounts found in sh liver oils, fatty sh species, whole egg, and beef liver (Ovesen et al. 2003). Vitamin D is a lipidsoluble prohormone obtained via de novo skin synthesis as a result of UV-light-induced photolytic conversion of 7-dehydrocholesterol to previtamin D3 followed by thermal isomerization to vitamin D3 or ingested through the diet. It is subsequently activated in a sequential two-step process (Holick and Adams 1998; Dusso and Brown 1998; Holick 2007) (Figure 11.1). The rst step is the 25-hydroxylation in the liver to produce 25(OH) vitamin D (25D). The second and more regulated step is the 1-hydroxylation, which is classically thought to occur primarily in the kidney via the 25-hydroxyvitamin D-1-alpha hydroxylase enzyme to produce the active product 1,25(OH)2 vitamin D3 (1,25D) or calcitriol (Holick and Adams 1998; Dusso and Brown 1998; Holick 2007). 1,25D binds to the vitamin D receptor (VDR), a nuclear receptor and a member of the steroid/ thyroid hormone superfamily receptors, which acts as a ligand-activated transcription factor. VDR functions as a heterodimer with the retinoid X receptor. Upon ligand binding the VDR undergoes a conformational change that promotes retinoid X receptor-VDR heterodimerization. The bound

Nutrition and Vitamin D................................................................................................................. 215 Clinical Epidemiology ................................................................................................................... 216 Mechanisms of Vitamin D Action .................................................................................................. 218 Classical and Nonclassical Functions of Vitamin D ...................................................................... 219 Genomic Effects of Vitamin D on Cardiovascular Disease ...........................................................220