title: Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response.
abstract: OBJECTIVE
  To investigate the possible association and gene-gene interaction effects of polymorphisms in NMDA receptor subunit (GRIN1, GRIN2A and GRIN2B) and dopamine receptor (DRD1, DRD2 and DRD3) genes with clozapine response.
  
  
  METHODS
  GRIN1 rs11146020 (G1001C), GRIN2A GT-repeat and GRIN2B rs10193895 (G-200T) polymorphisms were tested for association in a Caucasian (n = 183) and an African-American (n = 49) sample using χ(2) and ANOVA tests. Logistic regression and two-way ANOVA were used to explore gene-gene interaction effects with dopamine receptor gene variants.
  
  
  CONCLUSIONS
  This study does not support the involvement of the NMDA receptor subunit gene polymorphisms in clozapine response. All tests for an association were negative. Gene-gene interaction analyses however yielded promising leads, including an observed effect between DRD1 rs686 and DRD3 Ser9Gly polymorphisms on clozapine response (p = 0.002).
authors.affiliation: Neurogenetics Section, Centre for Addiction & Mental Health, 250 College Street, Toronto, Ontario, 5T1R8, Canada. rudirudi@gmail.com
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Renan P
authors.initials: RP
authors.lastname: Souza
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltze
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D004843:Epistasis, Genetic; D056726:Genetic Association Studies; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate