Immunophenotype of vitamin D receptor polymorphism associated to risk of HIV-1 infection and rate of disease progression.

Vitamin-D-receptor (VDR) mediates immunomodulatory effects of vitamin-D3 (VD3). The VDR-rs1544410_GG polymorphism has been associated with delayed progression rates to AIDS and resistance to HIV-1 infection. The aim of the present study was to investigate differences in VD3 mediated effects on rs1544410 genotyped dendritic cells (DCs) and macrophages (MDM), key cells involved in HIV-1 infection. Immature DCs exhibited lower b-actin-normalized VDR mRNA expression in rs1544410_GG compared to cells with a rs1544410_AA genotype. VD3 response on cell differentiation markers (CD14 inhibition and CD209 induction) was two-fold higher in rs1544410_AA (CD209, p=0.012; CD14, p=0.02). HIV-1-LTR reporter gene activity in MDM was boosted by VD3; however, the effect was up to 50% higher in rs1544410_AA. We conclude that the rs1544410_AA association with progression to AIDS and resistance to HIV-1 appears to be linked to an enhanced response to VD3.