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Common haplotypes in CD209 promoter and susceptibility to HIV-1 infection in intravenous drug users.

Common haplotypes in CD209 promoter and susceptibility to HIV-1 infection in intravenous drug users.
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Herrero R, Pineda JA, Rivero-Juarez A, Echbarthi M, Real LM, Camacho A, Macias J, Fibla J, Rivero A, Caruz A,


Herrero R, Pineda JA, Rivero-Juarez A, Echbarthi M, Real LM, Camacho A, Macias J, Fibla J, Rivero A, Caruz A, (click to view)

Herrero R, Pineda JA, Rivero-Juarez A, Echbarthi M, Real LM, Camacho A, Macias J, Fibla J, Rivero A, Caruz A,

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Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2016 8 1545() 20-25 pii 10.1016/j.meegid.2016.08.014

Abstract
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.

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