Vitamin D Binding Protein (Gc) Allele Variation Effects Response to Vitamin D Treatment

Vitamin D Status

Viatmin D, 25-hydroxyvitamin D, Vitamin D binding protein

We have just completed a randomized, clinical trial of 100,000 IU Vitamin D3 given as a single dose at the beginning of winter. We found a wide range of responses to the dose. This study proposes that genetic differences account for some of the variation in response of 25(OH)D levels after treatment with oral Vitamin D.

We suspect that the wide range of response is effected by other factors such as variation in Vitamin D binding protein (the major transporter of Vitamin D metabolites). Gc, also known as Vitamin D binding protein (DBP), group specific component, or Gc globulin, is a 52-58 kDa multifunctional plasma protein, synthesized in the liver. The gene encoding for Gc is located on chromosome 4, and three common co-dominant alleles give rise to three phenotypes (Gc1s, Gc1f, and Gc2). Gc binds actin, recruits neutrophil leukocytes and converts into a macrophage- and osteoclast- activating factor. It also is the major transporter of Vitamin D and its' metabolites. Lauridsen et al. showed that Gc phenotype correlates with 25(OH)D levels in a group of postmenopausal women. This study proposes that Gc phenotype accounts for some of the variation in response of 25(OH)D levels after treatment with oral Vitamin D.

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