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. 2012;7(2):e30990.
doi: 10.1371/journal.pone.0030990. Epub 2012 Feb 7.

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated With HIV-1-associated Dementia

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Free PMC article

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated With HIV-1-associated Dementia

Sebastiaan M Bol et al. PLoS One. .
Free PMC article

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Comparison of AIDS survival between HAD cases and non-HAD controls.
(A) Kaplan Meier analysis for time from AIDS to death with start cART as censor (vertical lines), for both HAD cases (grey line) and non-HAD AIDS patients as controls (black line). (B) Kaplan Meier analysis for time from AIDS to death with start cART as censor (vertical lines) for the controls (black line) and for time from AIDS to HAD for the HAD cases (grey line). cART, combination antiretroviral therapy; HAD, HIV-1-associated dementia.

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