Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2 supplementation

Background: It is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D-3 and 25(OH)D-2 in a Thai cohort, according to type of vitamin D supplement (vitamin D-3 or D-2) and DBP genotype, after receiving vitamin D-3 or D-2 for 3 months. Methods: Thirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D-3 or D-2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D-3 and 25(OH)D-2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR. Results: Vitamin D-3 supplementation of 400 IU/d increased 25(OH)D-3 significantly (+16.2 +/- 4.2 nmol/L, p < 0.001). Vitamin D-2 (400 IU/d) caused increased 25(OH)D-2 levels (+22.0 +/- 2.11 nmol/L, p < 0.001), together with a decrease of 25(OH)D-3 (-14.2 +/- 2.0 nmol/L, p < 0.001). At 3 month, subjects in vitamin D-3 group tended to have higher total 25(OH)D levels than those in vitamin D-2 (67.8 +/- 3.9 vs. 61.0 +/- 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D-3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D-3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D-2. Conclusion: Genetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D-3 but not vitamin D-2.