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Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals

Please always quote using this URN: urn:nbn:de:bvb:20-opus-132385
  • 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 thatDysfunction 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.show moreshow less

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Metadaten
Author: Anne Horn, Carsten Scheller, Stefan du Plessis, Gabriele Arendt, Thorsten Nolting, John Joska, Sieghart Sopper, Matthias Maschke, Mark Obermann, Ingo W. Husstedt, Johannes Hain, Tongai Maponga, Peter Riederer, Eleni Koutsilieri
URN:urn:nbn:de:bvb:20-opus-132385
Document Type:Journal article
Faculties:Fakultät für Mathematik und Informatik / Institut für Mathematik
Medizinische Fakultät / Institut für Virologie und Immunbiologie
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):Journal of Neural Transmission
Year of Completion:2013
Volume:120
Pagenumber:1411-1419
Source:Journal of Neural Transmission (2013) 120:1411–1419 DOI 10.1007/s00702-013-1086-x
DOI:https://doi.org/10.1007/s00702-013-1086-x
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:CSF; DAT; HAND; HIV; dopamine; polymorphism
Release Date:2016/06/11
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung