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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 .

Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2supplementation