title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning.
authors.affiliation: National Neurological AIDS Bank, Department of Neurology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. ajlevine@mednet.ucla.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: Robert
authors.initials: R
authors.lastname: Bilder
authors.forename: Paul
authors.initials: P
authors.lastname: Shapshak
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015704:CD4 Antigens; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics / Q000821:virology; D004252:DNA Mutational Analysis; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000235:genetics; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009068:Movement / Q000502:physiology; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D019966:Substance-Related Disorders / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015704:CD4 Antigens; D050483:Dopamine Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase
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