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Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS.

An, P and Wang, LH and Hutcheson-Dilks, H and Nelson, G and Donfield, S and Goedert, JJ and Rinaldo, CR and Buchbinder, S and Kirk, GD and O'Brien, SJ and Winkler, CA (2007) Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. PLoS pathogens, 3 (6).

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Abstract

Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4(+) T-cell loss (relative hazard = 3.7, p = 0.003) in African Americans. Among European Americans, these alleles were also associated with a significant trend to more rapid progression to AIDS in a multi-point categorical analysis (p = 0.005). Both SNPs showed differential nuclear protein-binding efficiencies in a gel shift assay. In addition, one SNP (SNP5) located in the 5' UTR previously shown to be associated with higher ex vivo HIV-1 replication was found to be more frequent in HIV-1-positive individuals than in those highly exposed uninfected individuals. These results implicate regulatory PPIA polymorphisms as a component of genetic susceptibility to HIV-1 infection or disease progression, affirming the important role of PPIA in HIV-1 pathogenesis.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
An, P
Wang, LH
Hutcheson-Dilks, H
Nelson, G
Donfield, S
Goedert, JJ
Rinaldo, CRRINALDO@pitt.eduRINALDO
Buchbinder, S
Kirk, GD
O'Brien, SJ
Winkler, CA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHolmes, Edward C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 June 2007
Date Type: Publication
Journal or Publication Title: PLoS pathogens
Volume: 3
Number: 6
DOI or Unique Handle: 10.1371/journal.ppat.0030088
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
PubMed ID: 17590083
Date Deposited: 12 Jul 2012 13:12
Last Modified: 30 Oct 2018 14:03
URI: http://d-scholarship.pitt.edu/id/eprint/12874

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