Single nucleotide polymorphism in gene encoding transcription factor prep1 is associated with HIV-1-associated dementia

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

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Article numbere30990
JournalPloS one
Volume7
Issue number2
DOIs
StatePublished - Feb 7 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Bol, S. M., Booiman, T., van Manen, D., Bunnik, E. M., van Sighem, A. I., Sieberer, M., Boeser-Nunnink, B., de Wolf, F., Schuitemaker, H., Portegies, P., Kootstra, N. A., & van't Wout, A. B. (2012). Single nucleotide polymorphism in gene encoding transcription factor prep1 is associated with HIV-1-associated dementia. PloS one, 7(2), [e30990]. https://doi.org/10.1371/journal.pone.0030990