ABSTRACT
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.
Subject(s)
Dendritic Cells/immunology , Genetic Predisposition to Disease , HIV Infections/genetics , HIV Infections/immunology , Macrophages/immunology , Polymorphism, Single Nucleotide , Receptors, Calcitriol/genetics , Cholecalciferol/metabolism , Dendritic Cells/metabolism , Disease Progression , Genes, Reporter , HIV Infections/virology , HIV Long Terminal Repeat , HIV-1/physiology , Humans , Immunophenotyping , Macrophages/metabolism , Signal Transduction , SpainABSTRACT
Vitamin D receptor (VDR) participates in multiple immune functions. Here, we determined whether VDR gene-sequence variations are associated with intersubject differences in the risk of acquiring human immunodeficiency virus type 1 (HIV-1) infection. We assessed this in 460 males exposed to HIV-1 by injection drug use (335 infected and 125 uninfected) and 124 seronegative healthy subjects. Multilocus logistic regression analysis revealed haplotypes for rs11568820, rs4516035, rs10735810, rs1544410, and rs17878969 polymorphisms showing association with protection to HIV-1 infection (odds ratio, 0.4 [95% confidence interval, 0.22-0.72]; P = .0025), which remained significant after correction for multiple testing. We infer that VDR haplotypes might influence the risk of HIV-1 acquisition.
