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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Association of polymorphisms in the LEDGF/p75 gene (PSIP1) with susceptibility to HIV-1 infection and disease progression
AIDS, Volume 25, No. 14, Year 2011
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Description
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. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Authors & Co-Authors
Madlala, Paradise
South Africa, Durban
University of Kwazulu-natal
Gijsbers, R.
Belgium, Leuven
Ku Leuven
Christ, Frauke
Belgium, Leuven
Ku Leuven
Hombrouck, Anneleen
Belgium, Leuven
Ku Leuven
Werner, Lise
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Mlisana, Koleka P.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
An, Ping
United States, Frederick
Saic-frederick
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Winkler, Cheryl Ann
United States, Frederick
Saic-frederick
Debyser, Zeger
Belgium, Leuven
Ku Leuven
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Statistics
Citations: 23
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1097/QAD.0b013e328349c693
e-ISSN:
14735571
Research Areas
Cancer
Environmental
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study