Original Research ARTICLE

Front. Genet., 19 August 2011 | http://dx.doi.org/10.3389/fgene.2011.00042

Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system

Katrin Sikk1*, Sulev Kõks2,3, Ursel Soomets3,4, Leonard C. Schalkwyk5, Cathy Fernandes5, Sulev Haldre1, Sten-Magnus Aquilonius6 and Pille Taba1
  • 1 Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia
  • 2 Department of Physiology, University of Tartu, Tartu, Estonia
  • 3 Centre for Translational Research, University of Tartu, Tartu, Estonia
  • 4 Department of Biochemistry, University of Tartu, Tartu, Estonia
  • 5 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, UK
  • 6 Section of Neurology, Department of Neuroscience, Uppsala University, Uppsala, Sweden

Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the “immunological disease” category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn–methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections.

Keywords: ephedrone, gene expression profiling, HIV, intravenous drug abuse, methcathinone, manganese

Citation: Sikk K, Kõks S, Soomets U, Schalkwyk LC, Fernandes C, Haldre S, Aquilonius S-M and Taba P (2011) Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system. Front. Gene. 2:42. doi: 10.3389/fgene.2011.00042

Received: 14 March 2011; Paper pending published: 27 April 2011;
Accepted: 22 June 2011; Published online: 19 August 2011.

Edited by:

Ruth Luthi-Carter, Ecole Polytechnique Fédérale de Lausanne, Switzerland

Reviewed by:

Don A. Baldwin, University of Pennsylvania, USA
John Hogenesch, University of Pennsylvania, USA

Copyright: © 2011 Sikk, Kõks, Soomets, Schalkwyk, Fernandes, Haldre, Aquilonius and Taba. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Katrin Sikk, Department of Neurology and Neurosurgery, University of Tartu, L.Puusepa 8, Tartu 51014, Estonia. e-mail: katrin.sikk@regionaalhaigla.ee