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Polymorphisms of SOCS-1 are associated with a rapid HIV progression rate

Hersberger, Martin ; Schlaepfer, Erika ; Buehler, Marco ; Bochud, Pierre-Yves ; Vernazza, Pietro ; Marti-Jaun, Jacqueline ; Nemeth, Johannes ; Zwahlen, Marcel ; Schmidlin, Kurt ; Speck, Roberto F

Lippincott Williams & Wilkins 2020-06

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  • Título:
    Polymorphisms of SOCS-1 are associated with a rapid HIV progression rate
  • Autor: Hersberger, Martin ; Schlaepfer, Erika ; Buehler, Marco ; Bochud, Pierre-Yves ; Vernazza, Pietro ; Marti-Jaun, Jacqueline ; Nemeth, Johannes ; Zwahlen, Marcel ; Schmidlin, Kurt ; Speck, Roberto F
  • Assuntos: Clinic for Infectious Diseases ; Medical Clinic ; Medicine & health ; Pharmacology (medical), Infectious Diseases
  • Notas: Hersberger, Martin; Schlaepfer, Erika; Buehler, Marco; Bochud, Pierre-Yves; Vernazza, Pietro; Marti-Jaun, Jacqueline; Nemeth, Johannes; Zwahlen, Marcel; Schmidlin, Kurt; Speck, Roberto F (2020). Polymorphisms of SOCS-1 are associated with a rapid HIV progression rate. Journal of Acquired Immune Deficiency Syndromes, 84(2):189-195.
    https://www.zora.uzh.ch/id/eprint/189425/
    10.1097/qai.0000000000002319
  • Descrição: Objectives: 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. Design and methods: 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. Results: 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. Conclusions: 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.
  • Editor: Lippincott Williams & Wilkins
  • Data de criação/publicação: 2020-06
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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