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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.
Affiliation
  • Hersberger M; Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
  • Schlaepfer E; Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
  • Buehler M; Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
  • Bochud PY; Service of Infectious Diseases and Institute of Microbiology, University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
  • Vernazza P; Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; and.
  • Marti-Jaun J; Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
  • Nemeth J; Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
  • Zwahlen M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
  • Schmidlin K; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
  • Speck RF; Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
J Acquir Immune Defic Syndr ; 84(2): 189-195, 2020 06 01.
Article in En | MEDLINE | ID: mdl-32097250
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.
Subject(s)

Full text: 1 Collection: 01-internacional Health context: 2_ODS3 Database: MEDLINE Main subject: HIV Infections / HIV-1 / Polymorphism, Single Nucleotide / Suppressor of Cytokine Signaling 1 Protein Type of study: Observational_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: J Acquir Immune Defic Syndr Year: 2020 Document type: Article

Full text: 1 Collection: 01-internacional Health context: 2_ODS3 Database: MEDLINE Main subject: HIV Infections / HIV-1 / Polymorphism, Single Nucleotide / Suppressor of Cytokine Signaling 1 Protein Type of study: Observational_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: J Acquir Immune Defic Syndr Year: 2020 Document type: Article