title: Association of BST-2 gene variants with HIV disease progression underscores the role of BST-2 in HIV type 1 infection.
abstract: We tested bone marrow stromal cell antigen 2 (BST-2) gene variants rs3217318, a 19-base-pair insertion/deletion polymorphism in the promoter region, and rs10415893, a tag single-nucleotide polymorphism in the 3' untranslated region, for their association with human immunodeﬁciency virus type 1 (HIV-1) infection and disease progression. The study included 356 subjects exposed to HIV-1 (185 with and 171 without infection) and 188 controls. The first decrease in the CD4(+) T-cell count to <200 cells/µL was used as the primary outcome, whereas the primary outcome plus initiation of any antiretroviral treatment was used as a secondary composite outcome. Association with progression was found for both rs3217318 and rs10415893, following an overdominant model. Diplotype analysis revealed faster progression to both outcomes for subjects carrying the Δ19_G/i19_A diplotype. Luciferase assay showed that a promoter sequence containing the i19 allele had the lowest expression levels, suggesting that i19 allele carriers could have less BST-2 expression, reducing their capability to retain viral particles. These results point to the relevance of BST-2 as a host genetic factor modifying HIV-1 disease progression.
authors.affiliation: Unitat de Genètica Humana, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Lleida, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Laplana
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Pineda
authors.forename: Teresa
authors.initials: T
authors.lastname: Puig
authors.forename: Joan
authors.initials: J
authors.lastname: Fibla
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; 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