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

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

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

Ping An,Li Hua Wang,Holli Hutcheson-Dilks,George Nelson,Sharyne Donfield,James J Goedert,Charles R Rinaldo,Susan Buchbinder,Gregory D Kirk,Stephen J O'Brien,Cheryl A Winkler,

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.

Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. Publishing Authors By Initials

P An,LH Wang,H Hutcheson-Dilks,G Nelson,S Donfield,JJ Goedert,CR Rinaldo,S Buchbinder,GD Kirk,SJ O'Brien,CA Winkler,

For similar genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research

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

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: PLoS pathogens

VOLUME: 3

Page Numbers: e88

Journal Abbreviation: PLoS Pathog.

ISSN: 1553-7374

DAY: 3

MONTH: Jun

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 101238921

Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Single Nucleotide

MESH TERMS: genetics

Chemical & Substance for Abstract: Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. Information

Substance Name: Cyclophilin A

Registry Number: EC 5.2.1.-

Grant and Affiliation Information for Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS.

AFFILIATION: Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, Maryland, United States of America.

Country: United States

AGENCY: United States NCI

GRANT: N01-CO-12400

ACRONYM: CO

MEDLINETA: PLoS Pathog

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