Introduction: CD209 is a receptor expressed in the dendritic cells involved in recognition of oligosaccharides present in several pathogens with a relevant impact on human health. SNPs located in the promoter region have been associated with HIV-1 susceptibility, although this finding has not been replicated in other populations. The objective of this study is to evaluate the association of CD209 promoter haplotypes with risk of HIV-1 infection in a cohort of Spanish male intravenous drug users (IDU) infected with hepatitis C virus (HCV) and to characterize the phenotypic effects of the associated variants.
Methods: We genotyped 4 SNPs of CD209 promoter in 295 HCV males exposed to HIV-1 infection by IDU, 165 HIV-1-infected and 130 exposed uninfected (EUI) and 142 healthy controls (HC). We have cloned the promoter variants in a reporter vector and evaluated the promoter activities in a cell culture model. CD209 mRNAs were measured in PBMC.
Results: Single-marker analysis revealed no significant allelic association with the risk of HIV-1 infection by parenteral route. Nevertheless, one haplotype was significantly overrepresented in EUI compared with HIV-1 positive patients and was associated with HIV-1 status (P=0.0008; OR: 0.43). Functional experiments suggested that the protective haplotype displayed lower transcriptional activity in vitro (P<0.05) and this was correlated with lower CD209 mRNA expression in PBMC (P=0.014).
Conclusions: This study suggests that the promoter haplotypes of CD209 influence the risk of HIV-1 acquisition in IDU and that this association is correlated with the mRNA expression level.
Keywords: CD209; DC-SIGN; HCV; HESN; HIV-1; IDU.
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