Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
Collaborative for Research on Outcomes and Metrics, Silver Spring, MD, USA.
Neurotox Res. 2021 Dec;39(6):1721-1731. doi: 10.1007/s12640-021-00406-1. Epub 2021 Oct 6.
Human immunodeficiency virus (HIV)-associated cognitive disorders (HAND) is characterized by impaired motor and intellectual functions, as well as mood disorders. Brain-derived neurotrophic factor and its receptor TrkB (or NTRK2) mediate the efficacy of antidepressant drugs. Genomic studies of BDNF/TrkB have implicated common single-nucleotide polymorphisms in the pathology of depression. In the current study, we investigated whether single-nucleotide polymorphisms (SNPs) (rs1212171, rs1439050, rs1187352, rs1778933, rs1443445, rs3780645, rs2378672, and rs11140800) in the NTRK2 has a functional impact on depression in HIV-positive subjects. We have utilized the Central Nervous System (CNS) HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Our methods explored the univariate associations of these SNPs with clinical (current and lifetime) diagnosis of depression via chi-square. The distribution of alleles was significantly different for African-Americans and Caucasians (non-Hispanic) for several SNPs, so our regression analyses included both "statistical controls" for race group and models for each group separately. Finally, we applied a method of simultaneous analysis of associations, estimating the mutually shared information across a system of variables, separately by race group. Our results indicate that there is no significant association between clinical diagnosis of major depression and these SNPs for either race group in any analysis. However, we identified that the SNP associations varied by race group and sex.
人类免疫缺陷病毒（HIV）相关认知障碍（HAND）的特征是运动和智力功能受损，以及情绪障碍。脑源性神经营养因子及其受体 TrkB（或 NTRK2）介导抗抑郁药的疗效。BDNF/TrkB 的基因组研究表明，常见的单核苷酸多态性与抑郁症的发病机制有关。在目前的研究中，我们调查了 NTRK2 中的单核苷酸多态性（SNP）（rs1212171、rs1439050、rs1187352、rs1778933、rs1443445、rs3780645、rs2378672 和 rs11140800）是否对 HIV 阳性患者的抑郁症有功能影响。我们利用了中枢神经系统（CNS）HIV 抗逆转录病毒治疗效果研究（CHARTER）队列。我们的方法通过卡方检验探索了这些 SNP 与临床（当前和终身）抑郁症诊断的单变量关联。对于几个 SNP，非洲裔美国人和白种人（非西班牙裔）的等位基因分布差异显著，因此我们的回归分析包括了种族群体的“统计对照”和分别为每个群体建模。最后，我们应用了一种关联的同时分析方法，分别按种族群体估算了变量系统之间的相互共享信息。我们的结果表明，在任何分析中，这两个种族群体的临床诊断为重度抑郁症与这些 SNP 之间均无显著关联。然而，我们发现 SNP 关联因种族群体和性别而异。
