期刊
PLOS PATHOGENS
卷 3, 期 6, 页码 849-857出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.0030088
关键词
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资金
- Intramural NIH HHS Funding Source: Medline
- NCATS NIH HHS [UL1 TR000005] Funding Source: Medline
- NCI NIH HHS [N01-CO-12400, N01CO12400] Funding Source: Medline
- NIDA NIH HHS [R01 DA004334, R37 DA004334, DA-04334, R56 DA004334] Funding Source: Medline
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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