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Host genetic polymorphisms in human immunodeficiency virus-related neurologic disease

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Abstract

The objective of this study was to determine whether host genetic polymorphisms influence the risk of developing human immunodeficiency virus (HIV) encephalitis and vacuolar myelopathy. Allelic association studies were carried out with common polymorphisms in candidate genes that are postulated to play a role in the pathogenesis of HIV-related neurologic complications. The authors studied brains and spinal cords from 270 patients who died of acquired immunodeficiency syndrome (AIDS) from 1989 to 1996. All had complete gross and microscopic pathologic evaluations, and the presence of microglial nodules, multinucleated giant cells, myelin pallor, and vacuolar myelopathy was assessed by an experienced neuropathologist who was blinded to the genotype. DNA was extracted from frozen brain samples, and determination of the presence of the APOE4, TNF-2, IL-1B*2, ILIRN*2 polymorphisms was determined by polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) mapping. The authors did not detect a consistent association between inheritance of candidate polymorphic alleles and the pathologic findings of HIV encephalitis or vacuolar myelopathy. Allelic association studies with candidate genes are powerful techniques that have the potential to contribute to understanding the pathophysiology of HIV-related neurodegeneration. This preliminary study, although including a substantial number of patients, was not sufficiently powered to exclude a modest but clinically significant effects. Future studies will require much larger sample sizes and technical advances to allow screening at larger number of candidate loci.

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Authors and Affiliations

  1. Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, 75390-9036, Dallas, TX, USA

    Ramon Diaz-Arrastia, Yunhua Gong & Cynthia J. Kelly

  2. Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA

    Benjamin B. Gelman

Authors
  1. Ramon Diaz-Arrastia
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  2. Yunhua Gong
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  3. Cynthia J. Kelly
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  4. Benjamin B. Gelman
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Corresponding author

Correspondence to Ramon Diaz-Arrastia.

Additional information

This work was supported by NIH grants R03 MH64889 and R01 AG17861 (to R.D.-A), and U01 AI46373, R24 MH59656, and R24 NS45491 (to B.B.G.)

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Diaz-Arrastia, R., Gong, Y., Kelly, C.J. et al. Host genetic polymorphisms in human immunodeficiency virus-related neurologic disease. Journal of NeuroVirology 10 (Suppl 1), 67–73 (2004). https://doi.org/10.1080/753312755

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  • DOI: https://doi.org/10.1080/753312755

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