Gene Expression in HIV-Associated Neurocognitive Disorders

Objectives: To identify differentially expressed (DE) genes in HIV-associated neurocognitive disorders (HAND) patients in comparison with HIV-infected patients without HAND and controls. Design: A meta-analysis of publicly available gene expression data from HIV postmortem brain tissue studies. Methods: We selected studies using clearly defined inclusion and exclusion criteria. Within study data preprocessing and individual analyses were performed for each brain region. The following meta-analytic methods were applied: combining P values, combining effect sizes with and without a permutation method. The DE genes were defined with a false discovery rate less than 5% using Benjamini–Hochberg method. Results: Our meta-analysis on 3 studies encompasses analyses of over 48 postmortem brains [25 HAND, 7 HIV encephalitis (HIVE), 8 HIV-infected patients, and 8 controls]. Overall, 411 genes in white matter were DE in HAND with HIVE patients when comparing with controls. Of these, 94 genes were significantly expressed in all statistical methods. These 94 genes participate in significant pathways such as immune system, interferon response, or antigen presentation. Sixty-six of the 94 genes were significantly upregulated with log2 intensities greater than 2-fold. Strong examples of the highly upregulated genes were PSMB8-AS1, APOL6, TRIM69, PSME1, CTSB, HLA-E, GPNMB, UBE2L6, PSME2, NET1, CAPG, B2M, RPL38, GBP1, and PLSCR1. Only BTN3A2 was expressed in HAND with HIVE patients as compared with HAND patients without HIVE. Conclusion: A number of genes were DE in our meta-analysis that were not identified in the individual analyses. The meta-analytic approach has increased statistical power for identifying DE genes in HAND.