ArticleJournal of acquired immune deficiency syndromes (1999)2019
COMT Val158Met Polymorphism, Cardiometabolic Risk, and Nadir CD4 Synergistically Increase Risk of Neurocognitive Impairment in Men Living With HIV.
Article in Journal of acquired immune deficiency syndromes (1999), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 11 citations in OpenAlex.
- Screening macrophage polarization genes in spinal cord injury as therapeutic targets.PloS one · 2026Article
- Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Cerebrospinal fluid profiles of targeted metabolomics on neurotransmitters in patients with post-neurosurgical bacterial meningitis.Frontiers in cellular and infection microbiology · 2025Article
- Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease.Cardiovascular toxicology · 2024Review
- Childhood trauma and genetic variation in theIBRO neuroscience reports · 2022Article
- Lower CSF homovanillic acid relates to higher burden of neuroinflammation and depression in people with HIV disease.Brain, behavior, and immunity · 2020Article
- COMT val158met genotype alters the effects of methamphetamine dependence on dopamine and dopamine-related executive function: preliminary findings.Psychiatry research · 2020Article
- Cerebrospinal Fluid Norepinephrine and Neurocognition in HIV and Methamphetamine Dependence.Journal of acquired immune deficiency syndromes (1999) · 2020Article
- The Effects of Low-Risk Drinking on Neurocognition Among Older Persons Living With HIV as Compared to Those Without HIV.Alcoholism, clinical and experimental research · 2020Article
- Genetic variation in alcohol dehydrogenase is associated with neurocognition in men with HIV and history of alcohol use disorder: preliminary findings.Journal of neurovirology · 2020Article
- Comorbid HIV infection and alcohol use disorders: Converging glutamatergic and dopaminergic mechanisms underlying neurocognitive dysfunction.Brain research · 2019Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe Val allele of the Val158Met single-nucleotide polymorphism of the catechol-o-methyltransferase gene (COMT) results in faster metabolism and reduced bioavailability of dopamine (DA). Among persons living with HIV, Val carriers display neurocognitive deficits relative to Met carriers, presumably due to exacerbation of HIV-related depletion of DA. COMT may also impact neurocognition by modulating cardiometabolic function, which is often dysregulated among persons living with HIV. We examined the interaction of COMT, cardiometabolic risk, and nadir CD4 on neurocognitive impairment (NCI) among HIV+ men.
methodsThree hundred twenty-nine HIV+ men underwent COMT genotyping and neurocognitive and neuromedical assessments. Cohort-standardized z scores for body mass index, systolic blood pressure, glucose, triglycerides, and high-density lipoprotein cholesterol were averaged to derive a cardiometabolic risk score (CMRS). NCI was defined as demographically adjusted global deficit score of ≥0.5. Logistic regression modeled NCI as a function of COMT, CMRS, and their interaction, covarying for estimated premorbid function, race/ethnicity, and HIV-specific characteristics. Follow-up analysis included the 3-way interaction of COMT, CMRS, and nadir CD4.
resultsGenotypes were 81 (24.6%) Met/Met, 147 (44.7%) Val/Met, and 101 (30.7%) Val/Val. COMT interacted with CMRS (P = 0.02) such that higher CMRS increased risk of NCI among Val/Val [odds ratio (OR) = 2.13, P < 0.01], but not Val/Met (OR = 0.93, P > 0.05) or Met/Met (OR = 0.92, P > 0.05) carriers. Among Val/Val, nadir CD4 moderated the effect of CMRS (P < 0.01) such that higher CMRS increased likelihood of NCI only when nadir CD4 <180. DISCUSSION: Results suggest a tripartite model by which genetically driven low DA reserve, cardiometabolic dysfunction, and historical immunosuppression synergistically enhance risk of NCI among HIV+ men, possibly due to neuroinflammation and oxidative stress.
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