Dataset Information

Association of Polymorphisms in the Regulatory Region of the Cyclophilin a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression.

ABSTRACT: BACKGROUND:Human cyclophilin A (CypA) encoded by peptidyl prolyl isomerase A gene (PPIA), enhances HIV-1 replication by aiding capsid uncoating. The association of genetic variation in the PPIA regulatory region with susceptibility to HIV-1 infection, disease progression, and gene expression among black South Africans at risk for infection or infected with HIV-1 is unknown. METHODS:We genotyped 539 participants from 2 longitudinal study cohorts of black South Africans at high risk for infection or infected with HIV-1 for PPIA regulatory single nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS:Minor allele (G) of SNP rs6850 (rs6850 G) significantly associated with higher viral loads (mean 4.85 versus 4.46 log copies/mL, P = 0.0006) and lower CD4 T-cell counts (mean 506 versus 557 cells/?L, P = 0.0256) during the acute phase of infection in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 cohort. Consistently, rs6850 G significantly associated with higher viral loads (mean 4.49 versus 4.01 log copies/mL, P < 0.0001) and lower CD4 T-cell counts (mean 442 versus 494 cells/?L, P = 0.0002) during the early chronic phase of infection in the CAPRISA 002 cohort; rs6850 G further associated significantly with rapid CD4 T-cell decline in the CAPRISA 002 cohort (P = 0.0481) and Sinikithemba chronic infection cohort (P = 0.0156). Interestingly, rs6850 G significantly associated with elevated CypA mRNA levels in HIV-1-positive individuals (P = 0.0061). CONCLUSIONS:These data suggest that rs6850 G enhances HIV-1 replication through upregulation of CypA expression following HIV-1 infection. The data support ongoing efforts to develop anti-HIV-1 drugs that block interaction of HIV-1 and cellular proteins.

SUBMITTER: Madlala P

PROVIDER: S-EPMC4942341 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Association of Polymorphisms in the Regulatory Region of the Cyclophilin a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression.

Madlala Paradise P Singh Ravesh R An Ping P Werner Lise L Mlisana Koleka K Abdool Karim Salim S SS Winkler Cheryl A CA Ndungʼu Thumbi T

Journal of acquired immune deficiency syndromes (1999) 20160801 5

<h4>Background</h4>Human cyclophilin A (CypA) encoded by peptidyl prolyl isomerase A gene (PPIA), enhances HIV-1 replication by aiding capsid uncoating. The association of genetic variation in the PPIA regulatory region with susceptibility to HIV-1 infection, disease progression, and gene expression among black South Africans at risk for infection or infected with HIV-1 is unknown.<h4>Methods</h4>We genotyped 539 participants from 2 longitudinal study cohorts of black South Africans at high risk ...[more]

PMID: 27088296

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Project description:Genetic polymorphism of viral receptors is relevant to risks of HIV-1 infection, while it is still under debated whether the polymorphism of SDF1, a unique ligand for HIV-1 coreceptor CXCR4, is associated with HIV susceptibility and AIDS disease progression. Therefore, we provided an updated quantitative assessment by meta-analysis from 16 case-control and 7 cohort studies.Articles reporting the relationship between SDF1 polymorphism and HIV susceptibility or AIDS progression were retrieved from PubMed, Embase and Ovid electronic databases up to Apr 2017. Data were pooled by odds ratios (ORs) for HIV-1 infection with 95% confidence intervals (CIs) and summary relative hazards (RHs) for AIDS progression with 95% CIs using 1987 Center for Disease Control (CDC) case definition of AIDS (CDC87) and 1993 Center for Disease Control (CDC) case definition of AIDS (CDC93) and death as endpoints.As a result, 16 studies regarding susceptibility to HIV-1 infection with 2803 HIV-infected patients and 3697 healthy individuals and 7 studies regarding disease progression with 4239 subjects were included in the meta-analysis. For risks of infection, no evidences indicated SDF1 polymorphism was associated with the risk of HIV-1 infection in all genetic models (recessive model: OR = 0.94, 95% Cl: 0.75-1.17; homozygous model: OR = 0.89, 95% Cl: 0.70-1.15; heterozygous model: OR = 1.06, 95% Cl: 0.83-1.35; allele model: OR = 0.95, 95% Cl: 0.79-1.13), Furthermore, we failed to find an delayed AIDS progression except in some specific cohorts including MACS cohorts (RH = 0.38, 95% Cl: 0.17-0.59 for time to AIDS; RH = 0.27, 95% Cl: 0.07-0.46 for time to death at the study entry).Overall, no significant association was found between SDF1 polymorphism and HIV susceptibility. A protective effect of SDF1 on AIDS progression and death was seen especially in two studies based on the same cohorts. In conclusion, SDF1 polymorphism exerts a moderate protective effect against AIDS disease deterioration in some specific populations.

Dataset Information

Association of Polymorphisms in the Regulatory Region of the Cyclophilin a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression.

Publications

Association of Polymorphisms in the Regulatory Region of the Cyclophilin a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression.

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