rs2228595
This is a synonymous variant in the GRM3 gene — it does not change the protein's amino acid sequence.
▶Research that mentions this SNP (4)
▶Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophreniaAssociationN=61Jeffrey R. Bishop et al.(2015)· Psychopharmacology
This pharmacogenetic study in 61 first-episode schizophrenia patients found that GRM3 rs1468412 TT genotype was associated with worsening spatial working memory performance after antipsychotic treatment (p=0.001, Cohen's d=0.75), while GRM3 rs6465084 AA genotype was associated with improved negative symptoms after treatment (p=0.046). No significant associations were found between COMT Val158Met or DRD2/ANKK1 variants and cognitive or symptom changes.
▶Genetic Association, Mutation Screening, and Functional Analysis of a Kozak Sequence Variant in the Metabotropic Glutamate Receptor 3 Gene in Bipolar DisorderAssociationN=2,251Radhika Kandaswamy et al.(2013)· JAMA Psychiatry
This genetic association and functional analysis study identified a rare Kozak sequence variant (rs148754219) in the GRM3 (metabotropic glutamate receptor 3) gene significantly associated with bipolar disorder in 1099 cases and 1152 controls (P=0.005, odds ratio 4.20). The variant was found in 1.7% of bipolar cases versus 0.3% of controls. Functional experiments demonstrated that the variant creates a novel transcription factor binding site and strongly suppresses translation of one GRM3 isoform, suggesting a mechanism for increased bipolar disorder risk.
▶Replication study and meta‐analysis of the genetic association of GRM3 gene polymorphisms with schizophrenia in a large Japanese case‐control populationAssociationN=7,712Talal Albalushi et al.(2008)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Replication study and meta-analysis of GRM3 gene polymorphisms (rs274622, rs1468412, rs2299225) in 1,916 Japanese schizophrenia patients and 1,915 controls found no associations with schizophrenia (allelic P=0.68-0.74). Meta-analysis of five case-control studies including >3,000 patients each also failed to support associations previously reported in Japanese and Chinese populations, with pooled odds ratios of 0.99 (rs1468412, P=0.87) and 1.01 (rs2299225, P=0.67).
▶Evidence for statistical epistasis between catechol-O-methyltransferase (COMT) and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of schizophreniaAssociationN=1,794Kristin K. Nicodemus et al.(2007)· Human Genetics
Case-control and family-based association study in 1,794 individuals (296 cases, 370 controls, and 296 families in NIMH sibling study; 501 cases and 627 controls in German sample) investigating statistical epistasis between COMT polymorphisms (rs2097603, rs4680/Val158Met, rs165599) and SNPs in candidate schizophrenia genes. Found significant gene-gene interactions: three RGS4 SNPs showed increased schizophrenia risk with COMT (LRT P-values 0.02-0.05), six G72/DAOA SNPs exhibited epistasis with COMT, three GRM3 SNPs showed interaction effects, and DISC1 SNPs interacted with COMT Val158Met. Main effects for most candidate genes were null, highlighting the importance of epistatic models in psychiatric genetics.
About GRM3
L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. [provided by RefSeq, Jul 2008]
View all GRM3 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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