P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder.
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.
Lucae
Susanne
S
The Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.
Salyakina
Daria
D
Barden
Nicholas
N
Harvey
Mario
M
Gagné
Bernard
B
Labbé
Michel
M
Binder
Elisabeth B
EB
Uhr
Manfred
M
Paez-Pereda
Marcelo
M
Sillaber
Inge
I
Ising
Marcus
M
Brückl
Tanja
T
Lieb
Roselind
R
Holsboer
Florian
F
Müller-Myhsok
Bertram
B
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
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7