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Regulatory Polymorphisms in the Cyclophilin A Gene, PPIA, Accelerate Progression to AIDS
PLos ONE
  • Ping An, National Cancer Institute at Frederick
  • Li Hua Wang, National Cancer Institute at Frederick
  • Holli Hutcheson-Dilks, National Cancer Institute at Frederick
  • George Nelson, National Cancer Institute at Frederick
  • Sharyne Donfield, Rho, Inc.
  • James J. Goedert, National Cancer Institute at Bethesda
  • Charles Rinaldo, University of Pittsburgh
  • Susan Buchbinder, San Francisco Department of Public Health
  • Gregory D. Kirk, Johns Hopkins University
  • Stephen J. O'Brien, National Cancer Institute at Frederick
  • Cheryl Winkler, National Cancer Institute at Frederick
Document Type
Article
Publication Date
7-1-2007
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.

Comments

This is an open-access article distributed under the terms of the Creative Commons Public Domain decalration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Additional Comments
National Cancer Institute contract #: N01-CO-124000; National Institute on Drug Abuse grant #: DA-04334
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Citation Information
Ping An, Li Hua Wang, Holli Hutcheson-Dilks, George Nelson, et al.. "Regulatory Polymorphisms in the Cyclophilin A Gene, PPIA, Accelerate Progression to AIDS" PLos ONE Vol. 3 Iss. 6 e88 (2007) p. 849 - 857 ISSN: 1932-6203
Available at: http://works.bepress.com/stephen-obrien/537/