Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia.
BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To id...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3274517?pdf=render |
| _version_ | 1818540453434228736 |
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| author | Sebastiaan M Bol Thijs Booiman Daniëlle van Manen Evelien M Bunnik Ard I van Sighem Margit Sieberer Brigitte Boeser-Nunnink Frank de Wolf Hanneke Schuitemaker Peter Portegies Neeltje A Kootstra Angélique B van 't Wout |
| author_facet | Sebastiaan M Bol Thijs Booiman Daniëlle van Manen Evelien M Bunnik Ard I van Sighem Margit Sieberer Brigitte Boeser-Nunnink Frank de Wolf Hanneke Schuitemaker Peter Portegies Neeltje A Kootstra Angélique B van 't Wout |
| author_sort | Sebastiaan M Bol |
| collection | DOAJ |
| description | BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders. |
| first_indexed | 2024-12-11T21:55:34Z |
| format | Article |
| id | doaj.art-39162ba0da244103989f1c69d89be247 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:55:34Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-39162ba0da244103989f1c69d89be2472022-12-22T00:49:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3099010.1371/journal.pone.0030990Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia.Sebastiaan M BolThijs BooimanDaniëlle van ManenEvelien M BunnikArd I van SighemMargit SiebererBrigitte Boeser-NunninkFrank de WolfHanneke SchuitemakerPeter PortegiesNeeltje A KootstraAngélique B van 't WoutBACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders.http://europepmc.org/articles/PMC3274517?pdf=render |
| spellingShingle | Sebastiaan M Bol Thijs Booiman Daniëlle van Manen Evelien M Bunnik Ard I van Sighem Margit Sieberer Brigitte Boeser-Nunnink Frank de Wolf Hanneke Schuitemaker Peter Portegies Neeltje A Kootstra Angélique B van 't Wout Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. PLoS ONE |
| title | Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. |
| title_full | Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. |
| title_fullStr | Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. |
| title_full_unstemmed | Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. |
| title_short | Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia. |
| title_sort | single nucleotide polymorphism in gene encoding transcription factor prep1 is associated with hiv 1 associated dementia |
| url | http://europepmc.org/articles/PMC3274517?pdf=render |
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