Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response

Rudi Hwang*, Renan P. Souza, Arun K. Tiwari, Clement C. Zai, Daniel J. Müller, Steven G. Potkin, Jeffrey A. Lieberman, Herbert Y. Meltzer, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Aims: 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. Materials & 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. Results & conclusion: 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).

Original languageEnglish (US)
Pages (from-to)277-291
Number of pages15
JournalPharmacogenomics
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2011

Keywords

  • GRIN1
  • GRIN2A
  • GRIN2B
  • NMDA receptor subunit gene
  • antipsychotic response
  • association study
  • clozapine response
  • dopamine receptor gene
  • gene-gene interaction
  • schizophrenia

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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