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The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders

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Abstract

Despite progress in the treatment of the Human Immunodeficiency virus (HIV), there continues to be a high prevalence of infected individuals who develop neurocognitive deficits and disorders. Our understanding of the potential cause of HIV-associated neurocognitive disorders (HAND) continues to develop on many fronts. Among them is the study of host genetics. Here, we review the most current information regarding the association between host genetics and risk for HIV infection, AIDS, and HAND. We focus on the role of dopamine dysfunction in the etiology of HAND, and propose a number of genetic polymorphisms within genes related to dopaminergic functioning and other neurobiological factors that may confer vulnerability or protection against HAND.

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Abbreviations

HIV:

Human immunodeficiency virus

HAND:

HIV-associated neurocognitive disorders

AIDS:

Acquired immunodeficiency syndrome

HACMC:

HIV-1-associated cognitive/motor complex

MCMD:

HIV-1-associated minor cognitive/motor disorder

HAD:

HIV-associated dementia

CNS:

Central nervous system

CCR:

Chemokine receptor

MCP-1:

Monocyte chemo attractant protein-1

HIVE:

HIV encephalitis

TNF:

Tumor necrosis factor

IL:

Interleukin

MRI:

Magnetic resonance imaging

fMRI:

Functional magnetic resonance imaging

MRS:

Magnetic resonance spectroscopy

PET:

Positron emission tomography

DA:

Dopamine

DAT1:

Dopamine transporter

DRD:

Dopamine receptor

CSF:

Cerebrospinal fluid

HAART:

Highly active antiretroviral therapy

GP:

Genetic polymorphism

mRNA:

Messenger ribonucleic acid

SDF-1:

Stromal cell-derived factor-1

RANTES:

Regulated upon Activation, Normal T-cell Expressed, and Secreted

COMT:

Catechol-O-methyltransferase

VNTR:

Variable nucleotide tandem repeat

ADHD:

Attention deficit/hyperactivity disorder

DBH:

Dopamine-beta-hydroxylase

BNDF:

Brain derived neurotrophic factor

ApoE:

Apolipoprotein E

DARPP-32:

Dopamine and cAMP-regulated phosphoprotein of molecular weight 32 kDa

NNTC:

National NeuroAIDS Tissue Consortium

MACS:

Multicenter AIDS Cohort Study

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Acknowledgements

Drs. Singer and Levine are supported by NINDS (NS-38841). Dr. Levine is also supported by the California HIV/AIDS Research Program (CHRP) Grant ID06-LA-187. Dr. Shapshak acknowledges support from NIH (GM056529, DA14533, and DA12580).

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Authors and Affiliations

  1. National Neurological AIDS Bank, Department of Neurology, University of California Los Angeles – David Geffen School of Medicine, 11645 Wilshire Blvd., Suite 770, Los Angeles, CA, 90025, USA

    Andrew J. Levine & Elyse J. Singer

  2. Departments of Psychiatry & Behavioral Medicine and Medicine (Division of Infectious Diseases), University of South Florida – College of Medicine, Tampa, FL, USA

    Paul Shapshak

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  1. Andrew J. Levine
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  2. Elyse J. Singer
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  3. Paul Shapshak
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Correspondence to Andrew J. Levine.

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Levine, A.J., Singer, E.J. & Shapshak, P. The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders. AIDS Behav 13, 118–132 (2009). https://doi.org/10.1007/s10461-008-9360-x

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  • DOI: https://doi.org/10.1007/s10461-008-9360-x

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