Abstract
Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.
Highlights
Materials and methodsHIV infection causes neurological and psychiatric complications manifesting in HIV-associated neurocognitive disorders (HAND) despite antiretroviral therapy (Mothobi and Brew 2012)
We demonstrate for the first time that people infected with HIV carry significantly more often the DA transporter (DAT) 10/10-repeat allele compared to uninfected subjects, indicating that this genotype confers a significant risk factor for HIV infection
The reason for studying both German and South Africa (SA) groups was that we initially identified the higher frequency of the DAT 10/10-repeat allele in our German cohort and we wanted to exclude that this could be a feature based on homosexuality as the German participants are men having sex with men
Summary
Materials and methodsHIV infection causes neurological and psychiatric complications manifesting in HIV-associated neurocognitive disorders (HAND) despite antiretroviral therapy (Mothobi and Brew 2012). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes.
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