rs724226
This variant is located in the GRM3 gene.
▶Research that mentions this SNP (5)
▶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.
▶Association of RANBP1 haplotype with smooth pursuit eye movement abnormalityReviewHyun Sub Cheong et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).
▶Association between type‐three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophreniaAssociationN=95Jeffrey R. Bishop et al.(2011)· Human Psychopharmacology: Clinical and Experimental
This candidate gene association study examined 95 treatment-refractory schizophrenia patients genotyped for seven GRM3 markers. Two SNPs (rs1989796 and rs1476455) at the 3' end of the gene were significantly associated with global psychosis symptoms measured by BPRS total scores (rs1476455: CC genotype 55.1±10.4 vs A-carriers 48.3±9.2, F=7.6, p=0.0071; rs1989796: CC genotype 50.1±5.7 vs T-carriers 55.8±10.5, F=7.1, p=0.0091), but not with negative symptoms.
▶Influence of neurexin 1 (NRXN1) polymorphisms in clozapine responseReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental
This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.
▶Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjectsReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental
A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.
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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