Publication
Polymorphisms of SOCS-1 are associated with rapid HIV progression rate
Journal Paper/Review - Feb 21, 2020
Hersberger Martin, Schmidlin Kurt, Zwahlen Marcel, Nemeth Johannes, Marti-Jaun Jacqueline, Vernazza Pietro, Bochud Pierre-Yves, Buehler Marco, Schlaepfer Erika, Speck Roberto F
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Brief description/objective
OBJECTIVES
Immune activation, among other driven by IFN-α and -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 -γ axis. Here, we analyzed the role of 9 single nucleotide polymorphisms (SNPs) within SOCS-1 and 3 genes for their association with 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 SOCS1 and -3 and with regards 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. In contrast, the minor TT genotype of rs33977706 is associated with twice the risk for rapid progression. No associations have been observed for the four SOCS-3 SNPs or the major SOCS-3 haplotypes.
CONCLUSION
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.