Genetic Predictor of Working Memory and Prefrontal Function in Women with HIV

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