Supplementary vitamin D3 and vitamin D receptor polymorphisms affect blood vitamin D levels in type-2 diabetes mellitus in Indonesia

   INTRODUCTION: There are no data on vitamin D receptor (VDR) gene single nucleotide polymorphism (SNP) influence on blood 25-hydroxy-cholecalciferol [25(OH)D] levels after supplementary vitamin D in Indonesian type 2 diabetes mellitus (T2DM) patients. This study evaluated the effects of the supplementary vitamin D3 and VDR gene SNPs rs1555410 and rs2228570 on blood 25(OH)D levels in T2DM cases.  METHODS: A randomized, double-blind placebo-controlled trial (RDPCT) was conducted at one research setting using 85 T2DM subjects divided into vitamin D group (VDG) and control group (CG) and receiving 5,000 IU/day vitamin D3 (cholecalciferol) or placebo once daily for 84 days. Levels of 25(OH)D were determined baseline and after supplementary vitamin D3 administration for 84 days. Circulatory 25(OH)D was assayed using ELISA. VDR polymorphisms were detected using sequencing.  RESULTS: Post-supplementary blood 25(OH)D rose appreciably from baseline in VDG for VDR rs1544410 genotypes G/G (p=0.001) and G/A (p=0.010), and in VDR rs2228570 genotypes T/T (p=0.012), T/C (p<0.001), and C/C (p=0.001). Post-supplementary VDG still contained 30.3% of subjects not reaching blood 25(OH)D ≥30 ng/mL.  In attaining blood 25(OH)D ≥30 ng/mL post-supplementation, VDR rs2228570 genotype T/C differed significantly from T/T (52.4% v. 100%; p=0.027), but there were no appreciable differences between genotypes C/C and T/T (78.6% v. 100%; p=0.273), as well as between VDR rs1544410 genotypes G/G and G/A (67.5% v. 100%; p=0.542).  CONCLUSION: Only 52.4% of subjects with VDR rs2228570 genotype T/C achieved sufficiently high blood 25(OH)D levels. VDR rs2228570 polymorphisms apparently influence T2DM response to supplementary vitamin D.