Functional polymorphisms in dopamine-related genes: Effect on neurocognitive functioning in HIV+ adults

Abstract

Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults. Method: A total of 184 HIV+ adults were included in the analysis. Three polymorphisms were examined within dopamine-modulating genes: COMT val158met, BDNF val66met, and the DAT 3′ variable number tandem repeat. Separate hierarchical regression analyses for five neurocognitive domains (working memory, processing speed, learning, memory, motor) were conducted. Predictor variables were age, ethnicity, gender, education, CD4+ T-cell count, current depression, genotype, and an interaction term capturing genotype and disease severity (CD4). Results: None of the polymorphisms or HIV disease variables significantly improved the hierarchical regression models. Younger age, higher education, and Caucasian ethnicity were almost invariably associated with better functioning across all five cognitive domains. A trend was noted for current depression as a predictor of motor and learning ability. Conclusion: This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning.

Keywords:

• Catechol-O-methyltransferase
• Brain-derived neurotrophic factor
• Dopamine transporter
• HIV-associated neurocognitive disorders
• NeuroAIDS
• Pharmacogenetic

Acknowledgments

This study was funded through the California HIV/AIDS Research Program grant ID06-LA-187, of which Dr Levine was the principal investigator. This study was also made possible through Grants U01-MH08021 and R24-NS38841 (National Neurological AIDS Bank), U01-MH083507 and R24-NS45491 (Texas Repository for AIDS Research), U01-MH083501 and R24-MH59724 (Manhattan HIV Brain Bank), U01-MH083506 and R24-MH59745 (California NeuroAIDS Tissue Network).