HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype

Sundermann, Erin E.; Bishop, Jeffrey R.; Rubin, Leah H.; Aouizerat, Bradley E.; Wilson, Tracey E.; Weber, Kathleen M.; Cohen, Mardge H.; Golub, Elizabeth T.; Anastos, Kathryn; Liu, Chenglong; Crystal, Howard; Pearce, Celeste Leigh; Maki, Pauline M.

doi:10.1097/qad.0b013e328361c6a1

Cited by 2 publications

(3 citation statements)

References 18 publications

(12 reference statements)

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“…HIV-infected women in this subsample were more likely to have a beneficial Met allele than HIV-uninfected women. The same Met allele frequency difference was previously found in comparisons between HIV-infected and uninfected women in the general WIHS population (Sundermann et al, 2013) demonstrating that this Met allele imbalance between serostatus groups generalizes to a population of multi-racial, low-income women and is not simply a sampling bias within this subsample. The higher proportion of Met allele carriers among HIV-infected women might be due to the positive association between Met allele and propensity for risk-taking (Bousman et al, 2010a; Amstadter et al, 2012; van den Bos et al, 2008).…”

Section: Discussionsupporting

confidence: 78%

“…As found in the WIHS more generally (Sundermann et al, 2013), more HIV-infected women carried the Met allele (67%) than HIV-uninfected women (37%), p =0.13. Therefore, the cognitively disadvantageous genotype was more prevalent among the HIV-uninfected (cognitively advantaged) group, an effect that might mask the negative effect of the Val/Val genotype and the positive effect of seronegativity.…”

Section: Resultssupporting

confidence: 52%

“…As in the behavioral study and in studies of HIV-infected women more generally (Sundermann et al, 2013), the distribution of COMT genotype differed by HIV serostatus (Χ 2 =7.9, p =0.005). Again, the proportion of carriers of the typically beneficial allele (Met) was significantly higher in HIV-infected women (65%) compared to HIV-uninfected women (38%), and the proportion of carriers of the Val allele was significantly higher in HIV-uninfected (62%) women compared to the HIV-infected woman (35%).…”

Section: Resultsmentioning

confidence: 65%

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Genetic predictor of working memory and prefrontal function in women with HIV

et al. 2014

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The Val158Met (rs4680) single nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1- and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared to HIV-uninfected women (p<0.05). A significant serostatus by genotype interaction (p<0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p<0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected, Val/Val carriers showed significantly greater prefrontal activation compared to HIV-uninfected, Val/Val carriers (p<0.01). Conversely, HIV-uninfected, Met allele carriers demonstrated significantly greater prefrontal activation compared to HIV-infected, Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

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Section: Discussionsupporting

confidence: 78%

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 65%

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Genetic predictor of working memory and prefrontal function in women with HIV

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Interactions of HIV and Drugs of Abuse

Hauser¹,

Knapp²

2014

International Review of Neurobiology

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Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome (neuroAIDS) and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain “connectome”. Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions.

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HIV serostatus differs by catechol-O-methyltransferase Val158Met genotype

Cited by 2 publications

References 18 publications

Genetic predictor of working memory and prefrontal function in women with HIV

Genetic predictor of working memory and prefrontal function in women with HIV

Interactions of HIV and Drugs of Abuse

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