ANALYSIS OF CLOZAPINE RESPONSE AND POLYMORPHISMS OF THE DOPAMINE D4 RECEPTOR GENE (DRD4) IN SCHIZOPHRENIC-PATIENTS

We have examined the hypothesis that a variable number of tandem repea ts in the third cytoplasmic loop of the dopamine D4 receptor influence s clinical response to clozapine using a sample of 189 schizophrenic p atients, Alleles of the 48-bp repeat, which range from two to ten copi es in the normal human population, were analysed by the polymerase cha in reaction using genomic DNA as template, Association between these a lleles and response to clozapine was tested using the difference in pr e- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and resp onse by analysis of variance. We conclude that the variation of the nu mber of 48-bp repeats alone does not determine response to clozapine, Larger studies are underway to determine if there is a more subtle rel ationship with sequence variation within the repeats or at other polym orphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors. (C) 1995 Wiley-Liss, Inc .