Gene–gene Interaction Analyses Between NMDA Receptor Subunit and Dopamine Receptor Gene Variants and Clozapine Response

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).