Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
J Acquir Immune Defic Syndr. 2020 Jun 1;84(2):189-195. doi: 10.1097/QAI.0000000000002319.
Immune activation, among others driven by interferon (IFN)-α and IFN-γ activation, is a main feature of progressive HIV infection. Suppressor of cytokine signaling (SOCS) 1 and 3 are negative feedback regulators of the IFN-α and IFN-γ axis. Here, we analyzed the role of 9 single-nucleotide polymorphisms (SNPs) within SOCS-1 and SOCS-3 genes for their association with an HIV progression rate in a cohort of 318 rapid vs 376 slow progressors from the Swiss HIV Cohort Study.
We analyzed 9 SNPs, which we have identified in Swiss blood donors, in a cohort of HIV-infected patients (n = 1144), which have been categorized according to the decline in CD4 T-cell counts. In all the conducted analyses, we focused on the comparison between rapid and slow progressors with regard to SNPs in SOCS-1 and SOCS-3 and with regard to haplotypes using multivariate logistic regression models.
Three SOCS-1 SNPs (rs193779, rs33989964, and rs4780355) are associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, are in strong linkage disequilibrium, forming a frequent haplotype. Homozygous carriers of this haplotype are also associated with a risk reduction for rapid progression. By contrast, the minor TT genotype of rs33977706 is associated with twice the risk for rapid progression. No associations have been observed for the 4 SOCS-3 SNPs or the major SOCS-3 haplotypes.
Our data suggest that SNPs in SOCS-1 are associated with HIV disease progression and speak in favor that immune activation is causal for the progressive immunodeficiency.
免疫激活是 HIV 感染进展的主要特征之一，干扰素（IFN）-α 和 IFN-γ 的激活是其主要原因。抑制细胞因子信号转导（SOCS）1 和 3 是 IFN-α 和 IFN-γ 轴的负反馈调节剂。在这里，我们分析了 SOCS-1 和 SOCS-3 基因内的 9 个单核苷酸多态性（SNP）与瑞士 HIV 队列研究中 318 名快速进展者和 376 名缓慢进展者的 HIV 进展率之间的关联。
我们分析了在瑞士献血者中发现的 9 个 SNP，这些 SNP 存在于感染 HIV 的患者队列（n=1144）中，这些患者根据 CD4 T 细胞计数的下降进行了分类。在所有进行的分析中，我们重点关注快速和缓慢进展者之间的比较，比较 SOCS-1 和 SOCS-3 中的 SNP 以及使用多元逻辑回归模型的单倍型。
SOCS-1 中的 3 个 SNP（rs193779、rs33989964 和 rs4780355）与快速进展的风险降低相关。这三个 SNP 中的两个，rs33989964 和 rs4780355，处于强连锁不平衡状态，形成了一个常见的单倍型。这种单倍型的纯合子携带者也与快速进展的风险降低相关。相反，rs33977706 的 TT 基因型是快速进展的两倍风险。SOCS-3 的 4 个 SNP 或主要 SOCS-3 单倍型没有观察到相关性。
我们的数据表明，SOCS-1 中的 SNP 与 HIV 疾病进展相关，并表明免疫激活是进行性免疫缺陷的原因。
