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Human Molecular Genetics Advance Access published online on July 5, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl166
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© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received March 21, 2006
Revised June 28, 2006
Accepted June 28, 2006

Article

P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder

Susanne Lucae 1, Daria Salyakina 1, Nicholas Barden 2, Mario Harvey 2, Bernard Gagné 2, Michel Labbé 2, Elisabeth B. Binder 1, Manfred Uhr 1, Marcelo Paez-Pereda 3, Inge Sillaber 3, Marcus Ising 1, Tanja Brückl 1, Roselind Lieb 1, Florian Holsboer 1, and Bertram Müller-Myhsok 1 *

1 Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
2 Neuroscience, CHUL Research Centre and Université Laval, 2705 Blvd. Laurier, Sainte-Foy, Quebec G1V 4G2, Canada
3 Affectis Pharmaceuticals, 80804 Munich, Germany

* To whom correspondence should be addressed.
Bertram Müller-Myhsok, E-mail: bmm{at}mpipsykl.mpg.de


  Abstract

The P2RX7 gene is located within a region on chromosome 12q24.31 that has been identified as a susceptibility locus for affective disorders by linkage and association studies. P2RX7 is a purinergic ATP-binding calcium channel expressed in neurons as well as in microglial cells in various brain regions. We investigated 29 single nucleotide polymorphisms (SNPs) within the P2RX7 gene and adjacent genes in a sample of 1000 German Caucasian patients suffering from recurrent major depressive disorder (MDD). These were contrasted with diagnosed healthy Caucasian controls from the same population (n = 1029). A non-synonymous coding SNP in the P2RX7 gene (rs2230912), previously found to be associated with bipolar disorder, was significantly associated (p = 0.0019) with MDD. This polymorphism results in an amino acid exchange in the carboxy-terminal cytosolic domain of the P2RX7 channel protein suggesting that the observed P2RX7 polymorphism might play a causal role in the development of depression.


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[Abstract] [Full Text] [PDF]


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