Gene Expression in HIV-Associated Neurocognitive Disorders: A Meta-Analysis

Area of Science:

• Neuroscience
• Genetics
• Immunology

Background:

• HIV-associated neurocognitive disorders (HAND) represent a significant neurological complication of HIV infection.
• Identifying specific gene expression changes in the brain is crucial for understanding HAND pathogenesis.

Purpose of the Study:

• To identify differentially expressed (DE) genes in the brain tissue of patients with HAND compared to HIV-infected individuals without HAND and controls.
• To leverage a meta-analytic approach to increase statistical power in detecting DE genes.

Main Methods:

• A meta-analysis of publicly available gene expression data from three postmortem brain tissue studies.
• Inclusion criteria were clearly defined, and data preprocessing was performed for each brain region.
• Meta-analytic methods included combining P values and effect sizes; DE genes were defined using a false discovery rate < 5%.

Main Results:

• The meta-analysis included 48 postmortem brains (25 HAND, 7 HIV encephalitis, 8 HIV-infected, 8 controls).
• 411 genes were differentially expressed in white matter of HAND with HIV encephalitis patients versus controls; 94 were significant across all methods.
• These 94 genes are involved in immune system, interferon response, and antigen presentation pathways, with 66 upregulated.

Conclusions:

• A meta-analytic approach identified DE genes not found in individual studies, demonstrating increased statistical power.
• The identified genes provide insights into the molecular mechanisms underlying HAND.