title: Common haplotypes in CD209 promoter and susceptibility to HIV-1 infection in intravenous drug users.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, 23071 Jaén, Spain. Electronic address: rocio.herrero.delrio@gmail.com.
authors.forename: Rocio
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit, Valme Hospital, 41014 Seville, Spain. Electronic address: japineda@telefonica.net.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, 14004 Cordoba, Spain. Electronic address: arjvet@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juarez
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, 23071 Jaén, Spain. Electronic address: echbarthi.meriem@gmail.com.
authors.forename: Meriem
authors.initials: M
authors.lastname: Echbarthi
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit, Valme Hospital, 41014 Seville, Spain. Electronic address: lmreal67b@gmail.com.
authors.forename: Luis-Miguel
authors.initials: LM
authors.lastname: Real
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, 14004 Cordoba, Spain. Electronic address: acamachoespejo@gmail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Camacho
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit, Valme Hospital, 41014 Seville, Spain. Electronic address: juan.macias.sanchez@gmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Macias
authors.affiliation: Human Genetics Unit, Department of Basic Medical Sciences, University of Lleida IRBLleida, 25003, Lleida, Catalonia, Spain. Electronic address: joan.fibla@cmb.udl.cat.
authors.forename: Joan
authors.initials: J
authors.lastname: Fibla
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, 14004 Cordoba, Spain. Electronic address: ariveror@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, 23071 Jaén, Spain. Electronic address: caruz@ujaen.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
mesh_terms: D000293:Adolescent; D000328:Adult; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D055030:Drug Users / Q000706:statistics & numerical data*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D015819:Substance Abuse, Intravenous / Q000150:complications / Q000453:epidemiology*; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: CD209; DC-SIGN; HCV; HESN; HIV-1; IDU