Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.
Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.
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DOI：
10.1097/qad.0000000000000604
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发表时间：
2015-04-24
期刊：
影响因子：
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通讯作者：
Johnson EO
中科院分区：
文献类型：
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作者：
Hancock DB;Gaddis NC;Levy JL;Bierut LJ;Kral AH;Johnson EO
骨髓基质细胞抗原2（BST 2）基因编码宿主限制因子，其充当HIV-1暴露的先天免疫传感器并抑制HIV-1颗粒的释放。我们的目的是确定BST 2基因区变异与HIV-1获得和疾病进展的关联。使用来自城市健康研究的HIV+病例和HIV-对照（N= 3，136名注射毒品的非洲裔美国人和欧洲裔美国人），我们测试了BST 2及其侧翼区域中的470种变体与HIV-1获得和对数转换病毒载量的相关性。我们发现单核苷酸多态性（SNP）rs 113189798超过了多重检验校正的P值阈值。rs 113189798-G等位基因（在非裔美国人中的频率为16%，在欧裔美国人中为4%）与HIV-1感染风险增加相关（荟萃分析P=1.43×10−4）：非裔美国人的比值比（95%置信区间）为1.22（1.01-1.49），欧裔美国人为2.17（1.43-3.33）。我们还发现，在我们的研究中，先前报道的rs 12609479-A等位基因（在非洲裔美国人中的频率=35%，在欧洲裔美国人中的频率= 81%）与获得HIV-1的风险降低名义上相关（荟萃分析P=0.036）。预计Rs 12609479-A可增加BST 2表达，从而降低获得HIV-1的风险。rs 113189798和rs 12609479仅弱相关（r2=0.2-0.4），代表不同的关联信号。在HIV+病例中，我们检测的变异体均与对数转换的病毒载量无显著相关性。我们的研究结果支持BST 2作为HIV-1获得的遗传易感因素：确定rs 13189798的新SNP关联，并将先前报道的调节SNP rs 12609479与HIV-1获得联系起来。
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. Using HIV+ cases and HIV- controls from the Urban Health Study (N=3,136 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. 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=1.43×10−4): 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 (r2=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+ cases. 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.