Association of polymorphisms in the LEDGF/p75 gene (PSIP1) with susceptibility to HIV-1 infection and disease progression.

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dc.creator Madlala, Paradise Z.
dc.creator Gijsbers, Rik.
dc.creator Christ, Frauke.
dc.creator Hombrouck, Anneleen.
dc.creator Werner, Lise.
dc.creator Mlisana, Koleka.
dc.creator An, Ping.
dc.creator Abdool Karim, Salim Safurdeen.
dc.creator Winkler, Cheryl A.
dc.creator Debyser, Zeger.
dc.creator Ndung'u, Thumbi.
dc.date.accessioned 2012-11-16T10:45:13Z
dc.date.available 2012-11-16T10:45:13Z
dc.date.created 2011
dc.date.issued 2011-06-10
dc.identifier.citation Madlala, P., et al. 2011. Association of Polymorphisms in the LEDGF/p75 Gene (PSIP1) with Susceptibility to HIV-1 Infection and Disease Progression. AIDS 25, pp.1711–1719. en
dc.identifier.issn 0269-9370
dc.identifier.uri http://dx.doi.org/DOI:10.1097/QAD.0b013e328349c693 en
dc.identifier.uri http://hdl.handle.net/10413/7874
dc.description.abstract Objective: LEDGF/p75, encoded by the PSIP1 gene, interacts with HIV-1 integrase and targets HIV-1 integration into active genes. We investigated the influence of polymorphisms in PSIP1 on HIV-1 acquisition and disease progression in black South Africans. Methods: Integrase binding domain of LEDGF/p75 was sequenced in 126 participants. Four haplotype tagging SNPs rs2277191, rs1033056, rs12339417 and rs10283923 referred to as SNP1, SNP2, SNP3 and SNP4, respectively, and one exonic SNP rs61744944 (SNP5, Q472L) were genotyped in 195 HIV-1 seronegative, 52 primary and 403 chronically infected individuals using TaqMan assays. LEDGF/p75 expression was quantified by real-time RT-PCR. The impact of Q472L mutation on the interaction with HIV_1 IN was measured by AlphaScreen. Results: rs2277191 (SNP1) A was more frequent among seropositives (P=0.06, Fisher’s exact test). Among individuals followed longitudinally SNP1A trended towards association with higher likelihood of HIV-1 acquisition [relative hazard (RH)=2.21, P=0.08; Cox model] and it was also associated with rapid disease progression (RH=5.98, P=0.04; Cox model) in the recently infected (primary infection) cohort. rs12339417 (SNP3)C was associated with slower decline of CD4+ T cells (P=0.02) and lower messenger RNA (mRNA) levels of LEDGF/p75 (P<0.01). Seroconverters had higher preinfection mRNA levels of LEDGF/p75 (P<0.01) and these levels decreased after HIV-1 infection (P=0.02). Conclusions: Genetic variants of PSIP1 may affect HIV-1 outcomes. Further studies are needed to confirm the effect of genetic variation of PSIP1 on HIV-1 pathogenesis in different cohorts. en
dc.language.iso en en
dc.publisher Lippincott Williams & Wilkins. en
dc.subject HIV infections--Genetic aspects--South Africa. en
dc.subject AIDS (Disease)--Genetic aspects--South Africa. en
dc.subject.other Lens epitheliumderived growth factor/p75 (LEDGF/p75) en
dc.subject.other PC4 or SFRS1 interacting protein 1 gene (PSIP1) en
dc.subject.other single nucleotide polymorphisms. en
dc.title Association of polymorphisms in the LEDGF/p75 gene (PSIP1) with susceptibility to HIV-1 infection and disease progression. en
dc.type Peer reviewed journal article en

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