Biology Faculty Articles
Document Type
Article
Publication Date
7-2007
Publication Title
PLos ONE
ISSN
1932-6203
Volume
3
Issue/No.
6 e88
First Page
849
Last Page
857
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.
Additional Comments
National Cancer Institute contract #: N01-CO-124000; National Institute on Drug Abuse grant #: DA-04334
NSUWorks Citation
An, Ping; Li Hua Wang; Holli Hutcheson-Dilks; George Nelson; Sharyne Donfield; James J. Goedert; Charles Rinaldo; Susan Buchbinder; Gregory D. Kirk; Stephen J. O'Brien; and Cheryl Winkler. 2007. "Regulatory Polymorphisms in the Cyclophilin A Gene, PPIA, Accelerate Progression to AIDS." PLos ONE 3, (6 e88): 849-857. https://nsuworks.nova.edu/cnso_bio_facarticles/780
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Included in
Genetics and Genomics Commons, Immunology and Infectious Disease Commons, Medicine and Health Sciences Commons
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.