Unitat de Genètica Humana, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Lleida, Spain.
J Infect Dis. 2013 Feb 1;207(3):411-9. doi: 10.1093/infdis/jis685. Epub 2012 Nov 12.
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.
我们测试了骨髓基质细胞抗原 2（BST-2）基因变体 rs3217318，这是启动子区域的 19 个碱基对插入/缺失多态性，以及 rs10415893，这是 3'非翻译区的标记单核苷酸多态性，以研究它们与人类免疫缺陷病毒 1（HIV-1）感染和疾病进展的关系。该研究包括 356 名接触 HIV-1 的受试者（185 名感染和 171 名未感染）和 188 名对照。将 CD4(+) T 细胞计数首次降至<200 个/µL 作为主要终点，而主要终点加上任何抗逆转录病毒治疗的开始作为次要复合终点。在超显性模型下，发现 rs3217318 和 rs10415893 与进展均有关联。双型分析显示，携带Δ19_G/i19_A 双型的受试者两种结局的进展都更快。萤光素酶检测显示，含有 i19 等位基因的启动子序列表达水平最低，这表明 i19 等位基因携带者的 BST-2 表达可能较少，从而降低了其保留病毒颗粒的能力。这些结果表明 BST-2 作为一种宿主遗传因素，可改变 HIV-1 疾病的进展。
