ABSTRACT

Nearly all of the circulating vitamin D metabolites are bound to serum proteins, mostly to vitamin D binding protein (VDBP). Vitamin D is primarily obtained through sunlight-induced synthesis, with typically smaller amounts coming from diet. Also, genetic variations affect steps in the vitamin D metabolic pathways, with heritability estimates for 25-hydroxyvitamin D (25(OH)D, the status indicator) from family studies ranging from 29% to 80% (Hunter et al. 2001, Shea et al. 2009, Wjst et  al. 2006). In our recent meta-analysis done in the context of the SUNLIGHT (Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits) Consortium, the gene coding the VDBP (group-specic component or Gc globulin, GC) was seen to exert the strongest effect on 25(OH)D concentrations (Wang et al. 2010). Differences between the carriers of GC risk allele and others were ~8 nmol/L, an effect size similar to that seen for the use of vitamin D supplementation in these types of population studies (Hyppönen and Power 2007). In this chapter, we provide

7.1 Introduction .................................................................................................. 107 7.2 Vitamin D Metabolism ................................................................................. 108

7.2.1 Genetic Effects on Vitamin D Metabolism ...................................... 108 7.2.2 The VDBP in the Metabolism Pathway of Vitamin D ..................... 110

7.2.2.1 Synthesis of Vitamin D Binding Protein ........................... 110 7.2.2.2 Group-Specic Component (GC) Gene ............................. 111

7.2.3 Associations of GC Variants with 25(OH)D and VDBP Concentrations .................................................................................. 112

7.3 Vitamin D and Cardiovascular Disease ....................................................... 112 7.3.1 Mechanisms ...................................................................................... 112 7.3.2 Observational Studies ....................................................................... 115 7.3.3 Intervention Studies .......................................................................... 116 7.3.4 VBDP Studies: Genetic and Measured Serum Concentrations ........ 117

7.4 Conclusions ................................................................................................... 119 References .............................................................................................................. 119

a short overview on vitamin D metabolism and the possible importance of vitamin D on cardiovascular disease, with a particular focus on evidence suggesting a role for vitamin D binding protein in mediating/altering these associations.