COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

Department of Psychiatry, University of California San Diego, La Jolla, CA 92103, USA.
Interdisciplinary Perspectives on Infectious Diseases 01/2010; 2010(10):678648. DOI: 10.1155/2010/678648
Source: PubMed


Catechol-O-methyltransferease (COMT) metabolizes prefrontal cortex dopamine (DA), a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior.

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    • "Since HIV patients have dopaminergic deficits, with decreased dopamine transporters [18, 19] and decreased cerebrospinal fluid dopamine and dopamine metabolites [62] , genetic variations in genes related to dopamine metabolism , such as LMX1A or catechol-O-methyltransferase, may modulate working memory training effects, BOLDfMRI results, and cerebrospinal fluid monoamine levels [55]. For instance, while HIV-positive subjects with the Met/Met alleles at the catechol-O-methyltransferase Val58- Met gene (a gene involved in the degradation of released dopamine) perform better on executive function [80], healthy individuals with the TT(AA) alleles at the LMX1A- rs4657412 benefit more from working memory training than those individuals with the C(G)-carrier [55] . Therefore , we predict that polymorphism of the LMX1A gene will differentially affect cognitive improvements among HIV-positive individuals. "

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