title: P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder.
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 C-terminal cytosolic domain of the P2RX7 channel protein, suggesting that the observed P2RX7 polymorphism might play a causal role in the development of depression.
authors.affiliation: The Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.forename: Daria
authors.initials: D
authors.lastname: Salyakina
authors.forename: Nicholas
authors.initials: N
authors.lastname: Barden
authors.forename: Mario
authors.initials: M
authors.lastname: Harvey
authors.forename: Bernard
authors.initials: B
authors.lastname: Gagné
authors.forename: Michel
authors.initials: M
authors.lastname: Labbé
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Marcelo
authors.initials: M
authors.lastname: Paez-Pereda
authors.forename: Inge
authors.initials: I
authors.lastname: Sillaber
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Tanja
authors.initials: T
authors.lastname: Brückl
authors.forename: Roselind
authors.initials: R
authors.lastname: Lieb
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D012008:Recurrence
chemical_list: C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7