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.
Torres
Carmen
C
Dpto. de Biología Experimental, Universidad de Jaén, Spain.
Sánchez de la Torre
Manuel
M
García-Moruja
Carelia
C
Carrero
Antonio José
AJ
Trujillo
María del Monte
Mdel M
Fibla
Joan
J
Caruz
Antonio
A
D002762:Cholecalciferol / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D015398:Signal Transduction; D013030:Spain
D018167:Receptors, Calcitriol; D002762:Cholecalciferol