P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder
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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.
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The Gln460Arg polymorphism in P2X7R has been suggested to affect Ca2+ influx, P2RX7 dimerization, and other protein-protein interactions having effects upon P2RX7-mediated signaling.
“The polymorphism causes an amino acid exchange from glutamine to arginine at position 460 (Gln460Arg) at long intracellular C-terminal domain of P2X7R, which have been suggested to affect both Ca2+ influx, P2RX7dimerization, and other protein—protein interactions having effects upon P2RX7-mediated signaling [71].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [71]
The non-synonymous coding SNP rs2230912 in the P2X7R gene is associated with MDD.
“Lucae et al. (2006) were the first to show the association of the non-synonymous coding single nucleotide polymorphisms (SNP) rs2230912 in the P2X7R gene with MDD [71].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [71]
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- Authors
- Lucae, S., Salyakina, D., Barden, N., Harvey, M., Gagné, B., Labbé, M., Binder, E. B., Uhr, M., Paez-Pereda, M., Sillaber, I., Ising, M., Brückl, T., Lieb, R., Holsboer, F., & Müller-Myhsok, B.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Müller-Myhsok, Bertram
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-05
- Volume
- 15
- Issue
- 16
- Pages
- 2438-2445
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2172099127
- Cited by
- 261
- References
- 49
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 4 · 2023: 10 · 2022: 10 · 2021: 12 · 2020: 8 · 2019: 6 · 2018: 15 · 2017: 9 · 2016: 10 · 2015: 16 · 2014: 17 · 2013: 18 · 2012: 23
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GS0481)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- P2X7 receptor, major depressive disorder, single nucleotide polymorphisms, genetic susceptibility, microglia, bipolar disorder, non-synonymous variants
- MeSH terms
- Adult, Major Depressive Disorder, Female, Gene Frequency, Genotype, Haplotypes, Humans, Genetic Linkage, Male, Middle Aged, Phenotype, Recurrence, Linkage Disequilibrium, Logistic Models, Case-Control Studies, Age of Onset, Receptors, Purinergic P2, Polymorphism, Single Nucleotide, Receptors, Purinergic P2X7
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