Host genetic polymorphisms in human immunodeficiency virus-related neurologic disease.
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.
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9036, USA. Ramon.diaz-Arrastia@UTSouthwestern.edu
Ramon
R
Diaz-Arrastia
Yunhua
Y
Gong
Cynthia J
CJ
Kelly
Benjamin B
BB
Gelman
D015526:AIDS Dementia Complex / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002490:Central Nervous System / Q000473:pathology / Q000502:physiology; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha