Investigation of promoter variations in dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) (CD209) and their relevance for human cytomegalovirus reactivation and disease after allogeneic stem-cell transplantation

Promoter variations in Toll-like receptor genes (n = 7) and genes encoding pathogen recognition and virus entry receptors (n = 7) were screened to detect any association with human cytomegalovirus (hCMV) reactivation and disease in patients following allogeneic stem-cell transplantation. Two single nucleotide polymorphisms (rs735240, G > A; rs2287886, C > T) in the promoter region of the dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) showed a significant association with an increased risk of development of hCMV reactivation and disease. Furthermore, these genetic markers influenced the expression levels of DC-SIGN on immature dendritic cells, as well as the infection efficiency of immature dendritic cells by hCMV, as determined by hCMV immediate-early antigen staining. Screening of patients following allogeneic stem-cell transplantation for the presence of these defined genetic polymorphisms might help to predict the individual risk of hCMV reactivation and disease.