Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D(3) or D(2) 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).