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• W2569456750 abstract "Abstract An intronic single nucleotide polymorphism (SNP) in RICH2 (rs2072255; 255 i ), in complete linkage disequilibrium (LD) with an exonic SNP (rs2072254; 254 e ), has been identified in a genome wide association study to be associated with progression to AIDS in Caucasian individuals. RICH2 links tetherin to the cortical actin network and the RICH2/tetherin interaction has been shown to be important for the downstream activation of NF-κβ and the consequential promotion of proinflammatory responses. We investigated the role of these two SNPs in natural control of HIV-1 in black South Africans including healthy controls (HCs; N = 102) and antiretroviral-naive HIV-1-infected controllers (HICs; N = 52) and progressors (N = 74). HICs were stratified as elite controllers (ECs; N = 11), viraemic controllers (VCs; N = 30), high viral load (VL) long term non-progressors (HVL LTNPs; N = 11) and also according to VL   400 RNA copies/ml (HICs VL > 400; N = 32). Results showed that in contrast to Caucasians who had very strong LD between these SNPs (r 2  = 0.97), black populations exhibited low LD (r 2  = 0.11–0.27), however a 254 e minor allele was always present with a 255 i minor allele but not vice versa. The SNPs did not show significant over- or underrepresentation in any particular group, however the combination of 254 e major allele homozygosity and 255 i heterozygosity (254 e AA/255 i GA) was underrepresented in HICs (OR = 3.26; P  = 0.04) and VCs (OR = 7.77; P  = 0.02) compared to HCs, and in HICs VL > 400 compared to both HCs ( P  = 0.002) and progressors ( P  = 0.02). A lower CD4 + T-cell count was associated with 254 e AA/255 i GA and 255 i (GA + AA) in the total HIV-1-infected group ( P  = 0.043) and progressors ( P  = 0.017), respectively. In silico analysis predicted loss of an exonic splice enhancer site with the 254 e -G allele. We postulate that altered splicing of RICH2 will affect levels of RICH2 expression and consequently NF-κβ activation. These findings point to a role for RICH2 and tetherin in viraemic natural control of HIV-1." @default.
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• W2569456750 date "2017-04-01" @default.
• W2569456750 modified "2023-10-17" @default.
• W2569456750 title "RICH2 is implicated in viraemic control of HIV-1 in black South African individuals" @default.
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• W2569456750 doi "https://doi.org/10.1016/j.meegid.2017.01.007" @default.
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