Polymorphisms of SOCS-1 are associated with rapid HIV progression rate.  Journal of Acquired Immune Deficiency Syndromes
Hersberger et al. aimed to investigate the role of 9 single-nucleotide polymorphisms (SNPs) within suppressor of cytokine signaling (SOCS) 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. Of note, SOCS 1 and 3 are negative feedback regulators of the IFN-a and IFN-g axis.
The authors analyzed 9 SNPs, which were identified in Swiss blood donors, in a cohort of HIV-infected patients (n = 1144), which were categorized according to the decline in CD4+ T-cell counts. In all the conducted analyses, they 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) were associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, were in strong linkage disequilibrium, forming a frequent haplotype. Homozygous carriers of this haplotype were also associated with a risk reduction for rapid progression. By contrast, the minor TT genotype of rs33977706 was associated with twice the risk for rapid progression. No associations were observed for the 4 SOCS-3 SNPs or the major SOCS-3 haplotypes.
In summary, SNPs in SOCS-1 are associated with HIV disease progression rate, speaking in favor that immune activation is causal for the progressive immunodeficiency. In addition, allelic variants of SOCS-1, with either decreased or increased transcriptional activity of SOCS-1, go along with slow and rapid progressor status, respectively. The latter findings imply that attenuating this specific pathway favors the HIV progression rate. Notwithstanding, we lack clinical studies, which specifically interfere with the IFN axis for ultimate proof of its pathogenic significance.