title: Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.
abstract: OBJECTIVE
  The bone marrow stromal cell antigen 2 (BST2) gene encodes a host restriction factor that acts as an innate immune sensor of HIV-1 exposure and suppresses release of HIV-1 particles. We aimed to identify associations of variants in the BST2 gene region with HIV-1 acquisition and disease progression.
  
  
  METHODS
  Using HIV+ cases and HIV- controls from the Urban Health Study (n=3136 African Americans and European Americans who inject drugs), we tested 470 variants in BST2 and its flanking regions for association with HIV-1 acquisition and log-transformed viral load.
  
  
  RESULTS
  We found that the single nucleotide polymorphism (SNP) rs113189798 surpassed the P value threshold corrected for multiple testing. The rs113189798-G allele (frequency=16% in African Americans, 4% in European Americans) was associated with increased HIV-1 acquisition risk (meta-analysis P=1.43 × 10): odds ratio (95% confidence interval) of 1.22 (1.01-1.49) in African Americans and 2.17 (1.43-3.33) in European Americans. We also found that the previously reported rs12609479-A allele (frequency=35% in African Americans, 81% in European Americans) was nominally associated with decreased risk of acquiring HIV-1 in our study (meta-analysis P=0.036). Rs12609479-A is predicted to increase BST2 expression and thereby decrease risk of acquiring HIV-1. Rs113189798 and rs12609479 were only weakly correlated [square of the correlation coefficient (r)=0.2-0.4] and represented distinct association signals. None of our tested variants were significantly associated with log-transformed viral load among the HIV-infected cases.
  
  
  CONCLUSIONS
  Our findings support BST2 as a genetic susceptibility factor for HIV-1 acquisition: identifying a novel SNP association for rs13189798 and linking the previously reported regulatory SNP rs12609479 to HIV-1 acquisition.
authors.affiliation: aBehavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division bResearch Computing Division, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina cDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri dUrban Health Program, Behavioral Health and Criminal Justice Division, RTI International, San Francisco, California eFellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, North Carolina, USA.
authors.forename: Dana B
authors.initials: DB
authors.lastname: Hancock
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Gaddis
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Levy
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Alex H
authors.initials: AH
authors.lastname: Kral
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D015703:Antigens, CD / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D015819:Substance Abuse, Intravenous / Q000150:complications*; D019562:Viral Load; D044465:White People; D055815:Young Adult; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2