Vitamin D binding protein (DBP) levels during tuberculosis treatment are affected by DBP genotype / haplotype but not by total vitamin D levels

Background: Vitamin D Binding Protein (DBP), also known as group specific component of serum (Gcglobulin) has been associated with susceptibility to tuberculosis. Its functions are varied including internalisation of vitamin D and conversion to macrophage activating factor (MAF). Single nucleotide polymorphisms (SNPs) at exon 11 (rs7041 and rs4588) result in GC1 and GC2 variants (GC1 subdivided into GC1S and GC1F). Methods: In an open label observational trial, patients with mycobacterial infection were supplemented with 100,000 units of cholecalciferol every 8 weeks and baseline bloods, vitamin D, DBP levels and various SNPs in the vitamin D axis were recorded. Results: In 49 active tuberculosis patients studied, the median vitamin D level was 12.1nmol/l. Vitamin D levels and DBP levels rose significantly (p<0.05) at each time interval and there was a significantly greater rise in DBP levels between weeks 0 and 8 in rs7041 TT homozygotes (p0.048). The finding may be reflective of the fact that it is more likely to produce GC1F variant. There was no other correlation found for any of the other SNPs analysed. There was no significant difference in baseline DBP levels in those who were severely deficient (25(OH)D levels <20nmol ) and those with levels >20nmol/l. This study shows that GC haplotype significantly affects the DBP level (p=0.022). Levels of DBP are higher with GC1S carriage and lower with GC1F carriage, with GC2 carriage DBP levels lying in between. Conclusion: Vitamin D does not influence DBP levels whilst genotype and haplotype influences DBP levels during mycobacterial infection.