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

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