title: Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia.
abstract: BACKGROUND
  Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies.
  
  
  METHODS
  We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested.
  
  
  RESULTS
  The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD.
  
  
  CONCLUSIONS
  These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sebastiaan M
authors.initials: SM
authors.lastname: Bol
authors.forename: Thijs
authors.initials: T
authors.lastname: Booiman
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Manen
authors.forename: Evelien M
authors.initials: EM
authors.lastname: Bunnik
authors.forename: Ard I
authors.initials: AI
authors.lastname: van Sighem
authors.forename: Margit
authors.initials: M
authors.lastname: Sieberer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boeser-Nunnink
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Peter
authors.initials: P
authors.lastname: Portegies
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Angélique B
authors.initials: AB
authors.lastname: van 't Wout
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics*; D016022:Case-Control Studies; D018932:Chemokine CCL2; D015658:HIV Infections / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D018398:Homeodomain Proteins; C106682:PKNOX1 protein, human; D019713:Receptors, CCR5