Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia.

Genetic polymorphisms in the regulatory regions of various cytokine genes influence the amount of cytokine produced in response to inflammatory stimuli. To determine whether such polymorphisms might play a role in human immunodeficiency virus (HIV) dementia, a disease process in which tumor necrosis factor (TNF)-alpha is believed to play a role, we analyzed HIV-infected adults with and without dementia and control populations for a polymorphic site located in the promoter region of the gene coding for TNF-alpha. The presence of the A allele at the TNF-alpha-308 site was overrepresented among adults with HIV dementia compared to those without dementia (0.28 vs 0.07; OR 5.5; 95% CI 1.8-17.0) and a healthy control population (0.28 vs 0.11). The increased frequency of the A allele in HlV-infected adults with dementia suggests that this locus may play a role in the pathophysiology of dementia and suggests a genetic predisposition for the development of HIV dementia.