The Association between Polymorphisms of Vitamin D Metabolic-Related Genes and Vitamin D(3) Supplementation in Type 2 Diabetic Patients

OBJECTIVE: To investigate the effect of single nucleotide polymorphisms (SNPs) of the key genes in vitamin D metabolic pathway on the serum 25(OH)D level after long-term vitamin D(3) supplementation and provide a theoretical basis for rational vitamin D(3) supplementation in diabetic patients with different genetic backgrounds. METHODS: Patients with type 2 diabetes (T2DM) who met the inclusive criteria were given 800 IU of vitamin D(3) daily for 30 consecutive months. Serum 25(OH)D levels was measured at enrollment and every 6 months after enrollment. The average value of four-time measurements represented individual serum 25(OH)D level during vitamin D(3) supplementation. Multiplex TaqMan genotyping was used to determine the distribution of eight candidate SNPs in genes of DHCR7, CYP2R1, CYP27B1, CYP24A1, and VDR, which are key genes in the vitamin D metabolic pathway, in diabetic patients. RESULTS: At baseline, the average serum 25(OH)D level was 22.71 ± 6.87 ng/mL, and 17.9% of patients had a ≥30 ng/mL level. During supplementation, the level of 25(OH)D increased significantly at each time point, and the average 25(OH)D level increased to 30.61 ± 5.04 ng/mL; however, there were 44.6% of patients whose serum 25(OH)D levels were still below 30 ng/mL. In the patients with CYP27B1 (rs10877012) G/T genotype, 71.79% achieved sufficient level of 25(OH)D, which was significantly higher than the other two genotypes (P < 0.05). Compared with those with T/T genotype, the RR of the patients with rs10877012 for <30 ng/mL level was 0.544 (95% CI: 0.291-0.917), and the RR after adjusting age and outdoor activity was 0.560 (95% CI: 0.292-0.970). CONCLUSION: The serum 25(OH)D level in patients with diabetes mellitus after long-term vitamin D(3) supplementation is associated with CYP27B1 polymorphism. Patients with rs10877012 G/T allele have a better response to vitamin D(3) supplementation. TRIAL REGISTRATION: This trial is registered with ChiCTR-IPC-17012657.